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pubmed_170_2401 | When conservative treatment is unsuccessful, there are many surgical options to treat patients with symptomatic chronic osteochondral lesions of the talus. The chosen treatment depends on the patient's symptoms, clinical examination findings, preoperative imaging results, and whether prior surgery was unsuccessful. It is important to be aware of treatment alternatives such as marrow stimulation, osteochondral autograft or allograft plugs, autologous chondrocyte implantation, and newer techniques currently being investigated outside the United States. | pubmed_170_2401 |
pubmed_453_12089 | Anti-SS-A/Ro antibodies are commonly found in systemic autoimmune diseases such as Sjögren's syndrome and systemic lupus erythematosus, and some of these antibodies appear to be responsible for certain pathological lesions including congenital heart block in neonatal lupus. In this study, we generated three human antibody Fab fragments that specifically bind to SS-A/Ro 60-kd peptide from salivary gland lymphocytes of a patient with Sjögren's syndrome by using a phage-display technique. Sequence analysis demonstrated that two of the three Fab clones (E-42 and E-60) used homologous heavy chains derived from the germline VH gene DP73 in combination with different light chains which were derived from germline V kappa gene L6 and V lambda gene DPL23. The third Fab clone (E-56) used another heavy chain derived from the germline VH gene DP31 in combination with the identical light chain as that of E-42. All three Fab clones revealed a high number of somatic mutations that likely occurred in the context of antigen selection. These findings suggest the restricted usage of VH and VL genes of anti-SS-A/Ro antibodies in salivary gland lymphocytes of the patient. | 10.1006/bbrc.1997.6233 |
pubmed_301_9007 | Most countries with endemic malaria have implemented national control programs. However there has been practically no change in the burden caused by malaria in zones of highest transmission, especially in Africa. Development of forms resistant to antimalarial agents suggests that adaptation of the treatment to the disease has not been adequately monitored, that insecticide-impregnated bednets and screens have not been used sufficiently, and that the vertical approach to these problems has destabilized a fragile health care system. Application of social anthropology could help to resolve these problems. The five main areas in which social anthropology could make a positive contribution can be summarized as follows: (1) improving mutual understanding between the population and heath care providers by describing popular systems for interpreting the disease; (2) describing available care services and popular healing practices as a means of understanding the reasoning underlying access to care; (3) analysing the implications of recommended preventive measures for social behavior (e.g. "bed manners") that must take into account the modalities of appropriation of the proposed innovations; (4) improving the relationship between care givers and patients by evaluating local moral perceptions; and (5) reducing the adverse effects of oververticalization of control programs by promoting opportunities for synthesis with projects initiated by community groups and local officials. By undertaking work on these problem areas, preliminary and permanent pluridisciplinary teams could improve the current situation. | pubmed_301_9007 |
pubmed_632_1381 | BACKGROUND
The PREFER study was an assessment of medication tolerability, treatment preference and symptom improvement during treatment with mirabegron (M) and tolterodine (T) extended release (ER) in patients with overactive bladder (OAB). In this analysis of PREFER, patient-reported outcomes (PROs) were assessed during treatment.
METHODS
PREFER was a two-period, 8-week crossover, double-blind, phase IV study (NCT02138747) of treatment-naïve adults with OAB ≥3 months randomized to 1 of 4 treatment sequences (M/T; T/M; M/M; T/T), separated by a 2-week washout. Tolterodine ER was dosed at 4 mg for 8 weeks and mirabegron was dosed at 25 mg for 4 weeks then increased to 50 mg for the next 4 weeks. At each visit, PROs related to treatment satisfaction, quality of life and symptom bother were assessed using the OAB Satisfaction (OAB-S; 3 independent scales/5 single-item overall assessments), OAB-q (total health-related QoL [HRQoL] and subscales [Sleep, Social, Coping, Concern] and Symptom Bother scale) and Patient Perception of Bladder Condition (PPBC) questionnaires. Responder rates were reported for OAB-q subscales based on a minimal important difference (MID; ≥ 10-point improvement) and OAB-S Medication Tolerability score ≥ 90.
RESULTS
In total, 358 randomized patients received ≥1 dose of double-blind study medication and completed ≥1 post-baseline value (OAB-S scale, OAB-q, PPBC): M/T (n = 154), T/M (n = 144), M/M (n = 30) or T/T (n = 30). At end of treatment (EoT), mirabegron and tolterodine ER were associated with similar mean improvements in 7 of the 8 OAB-S scores investigated, OAB-q scales and PPBC. A higher percentage of patients achieved clinically relevant improvements (MID) in OAB-q scales and OAB-S Medication Tolerability score during treatment with mirabegron than tolterodine ER.
CONCLUSIONS
On average, patients with OAB experienced improvements in treatment satisfaction, HRQoL and symptom bother that were of a similar magnitude during treatment with mirabegron or tolterodine ER. However, during mirabegron treatment, patients were more likely to achieve clinically relevant improvements in tolerability and HRQoL (as measured by the MID for the OAB-q or an OAB-S Medication Tolerability score ≥ 90) than during tolterodine ER treatment.
TRIAL REGISTRATION
NCT02138747 ; registered May 13, 2014. | 10.1186/s12955-018-0892-0 |
pubmed_641_10611 | Peptic ulcer disease (PUD) is a common cause of admission to hospital. Every year, there are approximately 30,000 admissions to hospital for upper gastrointestinal tract (GT) haemorrhage. Older people are at risk due to tissue changes in the tract associated with age. Younger sufferers may find that peptic ulcer disease is strongly related to lifestyle. Contributory factors include the level of emotional stress experienced, the type of food eaten and the variety/amount of stimulants taken. Peptic ulcers are medically treated with drugs from three different groups: antacids, mucosal protective agents and inhibitors of gastric secretion. Ulcers often recur after treatment, perhaps because of noncompliance with treatment or because a stressful lifestyle is resumed after healing has occurred. To achieve freedom from peptic ulcer disease, patients require from nurses not only information about their drug regime to encourage compliance, but health education to help them eliminate stressors that may contribute to the persistence of PUD. | pubmed_641_10611 |
pubmed_57_2719 | Key circulating molecules that link vitamin D (VD) to pediatric obesity and its co-morbidities remain unclear. Using a proteomic approach, our objective was to identify key molecules in obese children dichotomized according to 25OH-vitamin D (25OHD) levels. A total of 42 obese children (M/F = 18/24) were divided according to their 25OHD3 levels into 25OHD3 deficient (VDD; n = 18; 25OHD<15 ng/ml) or normal subjects (NVD; n = 24; >30 ng/ml). Plasma proteomic analyses by two dimensional (2D)-electrophoresis were performed at baseline in all subjects. VDD subjects underwent a 12mo treatment with 3000 IU vitamin D3 once a week to confirm the proteomic analyses. The proteomic analyses identified 53 "spots" that differed between VDD and NVD (p<0.05), amongst which adiponectin was identified. Adiponectin was selected for confirmational studies due to its tight association with obesity and diabetes mellitus. Western Immunoblot (WIB) analyses of 2D-gels demonstrated a downregulation of adiponectin in VDD subjects, which was confirmed in the plasma from VDD with respect to NVD subjects (p<0.035) and increased following 12mo vitamin D3 supplementation in VDD subjects (p<0.02). High molecular weight (HMW) adiponectin, a surrogate indicator of insulin sensitivity, was significantly lower in VDD subjects (p<0.02) and improved with vitamin D3 supplementation (p<0.042). A direct effect in vitro of 1α,25-(OH)2D3 on adipocyte adiponectin synthesis was demonstrated, with adiponectin and its multimeric forms upregulated, even at low pharmacological doses (10(-9) M) of 1α,25-(OH)2D3. This upregulation was paralleled by the adiponectin interactive protein, DsbA-L, suggesting that the VD regulation of adiponectin involves post-transciptional events. Using a proteomic approach, multimeric adiponectin has been identified as a key plasma protein that links VDD to pediatric obesity. | 10.1371/journal.pone.0083685 |
pubmed_794_18312 | BACKGROUND
International and national oncology societies had released recommendations in favor of COVID-19 vaccination in cancer patients. In the context of the national vaccination campaign targeting the so called extremely vulnerable, we aimed to assess the safety and efficacy of the mRNA vaccines in a cohort of 623 patients.
METHODS
Between March 26 and April 04, 2021, the Pfizer and BioNTech BNT162b2 mRNA and the Moderna mRNA-1273 vaccines were given as a two-dose prime-boost regimen. Starting on September 25th 2021 a third dose was offered to patients in whom a suboptimal immunogenicity with COVID-19 vaccination could be expected. Safety assessments were performed by phone call 7 days after each dose. Electronic health records were accessed to review demographic information, disease history, treatment detail, and outcome events of participants patients'.
FINDINGS
No toxicities were reported in 63.7%, 54%, and in 48.7% patients with cancer after each dose. Mild-to-moderate pain at the injection site was the most commonly adverse event. After the second dose, 46% of the 610 patients reported toxicity, with more systemic side-effects observed. Fever was reported in 45% of patients, with a temperature ≥ 38 °C in 21.4% of them. Of the 335 patients receiving a third vaccine dose, 51% reported toxicity, with 13% of patients reporting more than one effect. Logistic regression analysis reported mixed results, with limited variables or categories reporting a significant odd ratio. The type of vaccine reported a significant value at first dose (OR = 0.12; CI 0.52, 0.26; p = 0.00). Thirty-four cases of COVID-19 infection were reported with only one patient requiring a short-term hospitalization for monitoring.
INTERPRETATION
The safety profile of the mRNA vaccines does not raise any specific concerns and support prioritization of vaccination for cancer patients. | 10.1016/j.ejca.2022.04.008 |
pubmed_921_18007 | In the non-obese diabetic (NOD) mouse model of Type 1 (insulin-dependent) diabetes, evidence suggests that pancreatic beta cells are destroyed in part by apoptotic mechanisms. The precise mechanisms of beta cell destruction leading to diabetes remain unclear. The NOD mouse has been studied to gain insight into the cellular and molecular mediators of beta cell death, which are discussed in this review. Perforin, secreted by CD8(+) T cells, remains one of the only molecules confirmed to be implicated in beta cell death in the NOD mouse. There are many other molecules, including Fas ligand and cytokines such as interferon-gamma, interleukin-1 and tumor necrosis factor-alpha, which may lead to beta cell destruction either directly or indirectly via regulation of toxic molecules such as nitric oxide. As beta cell death can occur in the absence of perforin, these other factors, in addition to other as yet unidentified factors, may be important in the development of diabetes. Effective protection of NOD mice from beta cell destruction may therefore require inhibition of multiple effector mechanisms. | 10.1002/1520-7560(200007/08)16:4<251::aid-dmrr126>3.0.co;2-c |
pubmed_650_17938 | Two cases of aseptic osteochondrosis ischiopubica in a 6-years-old girl and a 10-years-old boy have been presented. In the described cases the radiological and clinical picture was the reason of diagnostic difficulties suggesting diagnosis of tumor and hematogenic osteitis. | pubmed_650_17938 |
pubmed_933_10279 | The mechanism of the association between breast cancer and obesity remains unknown. To investigate this mice over-expressing HER2/Neu in the mammary gland (MMTV-HER2/Neu) were fed either a high-fat diet (45% of calories) (HFD) or low-fat diet (10%) (LFD) from 4 weeks of age and followed for up to 1 year, or sacrificed when a mammary tumor reached 1.5 cm. There was a small but significant increase in body weight on HFD (P < 0.05) and the HFD mice displayed a greater fat mass determined by MRI (P < 0.01). Mild glucose intolerance was observed from 3 months of age on HFD, but insulin levels were not elevated. While the time of onset of a first tumor and tumor growth rates were not altered, mice on HFD had an earlier onset of a second tumor and a twofold greater incidence (LFD 25%, HFD 54%) and a greater absolute number of multiple tumors (tumors/mouse, LFD 1.5 +/- 0.25 vs. HFD 2.7 +/- 0.23, P < 0.01). Consistent with a lack of hyperinsulinemia, immunoblotting of skeletal muscle lysates from mice injected with insulin showed no insulin resistance determined by the phosphorylation of Akt/PKB. Similarly, there was no difference in basal or maximum insulin-stimulated phosphorylation of IRS-1/2, Akt/PKB, or p70 S6K in tumor cell lysates from HFD and LFD groups. Immunohistochemistry revealed no difference in tumor tissue staining for the proliferative marker, Ki67, between diets. These data indicate that HFD, in the absence of significant insulin resistance, mediates a tumor promoting, but not a tumor growth effect in this model of mammary carcinogenesis. | 10.1007/s10549-009-0586-8 |
pubmed_433_15503 | BACKGROUND
Activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) is established as a central intracellular trigger for various cardiac pathologies such as hypertrophy, heart failure or arrhythmias in animals and humans suggesting CaMKII as a promising target protein for future medical treatments. However, the physiological role of CaMKII is scarcely well defined.
AIM & METHODS
To investigate the role of CaMKII in hyperacute pressure overload, we evaluated the effects of pressure overload induced by transverse aortic constriction (TAC) on survival, cardiac function, protein expression and excitation-contraction coupling (ECC) in female WT littermate vs. AC3-I mice 2 days after TAC (2d post TAC). AC3-I mice express the CaMKII inhibitor autocamtide-3 related inhibitory peptide (AiP) under the control of the α-myosin heavy chain promotor in the heart.
RESULTS
CaMKII activation is significantly increased in WT TAC vs. sham mice 2d post TAC. Interestingly, survival is significantly reduced in AC3-I animals within the first five days after TAC compared to WT TAC littermates, while systolic cardiac function is markedly reduced in AC3-I TAC vs. AC3-I sham mice, but preserved in WT TAC vs. WT sham mice. Proteins regulating ECC such as ryanodine receptors (RyR2) and phospholamban (PLB) are hypophosphorylated at their CaMKII phosphorylation site in AC3-I TAC mice, but hyperphosphorylated in WT TAC mice compared to controls. In isolated cardiomyocytes fractional shortening is significantly impaired in AC3-I compared to WT mice 2d post TAC, and CaMKII incubation with AiP mimics the AC3-I phenotype in cardiomyocytes from WT TAC mice in vitro. In summary, this suggests cardiac dysfunction due to CaMKII inhibition as a potential cause of increased mortality in AC3-I TAC mice. However, proarrhythmic spontaneous Ca2+ release events (SCR) appear less frequent in cardiomyocytes from AC3-I TAC mice than in WT TAC mice.
CONCLUSIONS
Our data indicate that excessive CaMKII inhibition as present in AC3-I transgenic mice leads to an impaired adaptation of ECC to hyperacute pressure overload resulting in diminished cardiac contractility and increased death. Thus, our data suggest that in pressure overload the activation of CaMKII is a pivotal, but previously unknown part of hyperacute stress physiology in the heart, while CaMKII inhibition, albeit potentially antiarrhythmic, can be detrimental. This should be taken into account for future studies with CaMKII inhibitors as therapeutic agents. | 10.1016/j.yjmcc.2019.12.002 |
pubmed_285_9881 | This article examines acid-base balance and the interpretation of arterial blood gases (ABG). The article begins with a brief revision of related physiology, followed by a description of the primary disorders associated with acid-base imbalance. The normal ranges and the significance of abnormal ABG results are explored. The article concludes by providing an easy to follow four-step guide to ABG interpretation with practice examples presented in the CPD task section. | 10.1177/175045891502500304 |
pubmed_377_2962 | BACKGROUND/AIMS
Many complex diseases show a diversity of inheritance patterns ranging from familial disease, manifesting with autosomal dominant inheritance, through to simplex families in which only one person is affected, manifesting as apparently sporadic disease. The role of ascertainment bias in generating apparent patterns of inheritance is often overlooked. We therefore explored the role of two key parameters that influence ascertainment, penetrance and family size, in rates of observed familiality.
METHODS
We develop a mathematical model of familiality of disease, with parameters for penetrance, mutation frequency and family size, and test this in a complex disease: amyotrophic lateral sclerosis.
RESULTS
Monogenic, high-penetrance variants can explain patterns of inheritance in complex diseases and account for a large proportion of those with no apparent family history. With current demographic trends, rates of familiality will drop further. For example, a variant with penetrance 0.5 will cause apparently sporadic disease in 12% of families of size 10, but 80% of families of size 1. A variant with penetrance 0.9 has only an 11% chance of appearing sporadic in families of a size similar to those of Ireland in the past, compared with 57% in one-child families like many in China.
CONCLUSIONS
These findings have implications for genetic counselling, disease classification and the design of gene-hunting studies. The distinction between familial and apparently sporadic disease should be considered artificial. | 10.1159/000330167 |
pubmed_617_2363 | BACKGROUND
Hyperplasia of mammary glands (HMG) is a frequent disease, with increased cancer risk for women aged 20-55 years. The aim of this study was to explore a non-invasive method to identify which patients with breast complaints need additional mammography for HMG diagnosis.
PATIENTS AND METHODS
Skin digital infrared thermal imaging (DITI) in 74 patients with HMG and 63 controls was carried out.
RESULTS
In the controls, the temperature of points close to the breasts and ovaries decreased with age. In women older than 39 years, HMG patients showed persistently high temperatures but in the lower extremities there were no differences. With a threshold for thoracic skin point KI21 of 33.2 degrees C, sensitivity and specificity in distinguishing controls from HMGs were 96% and 52% (p=0.0001) respectively, as validated in a test set, similar to recent DITI results for breast cancer detection.
CONCLUSION
Infrared temperature imaging of specific skin points is a rapid, non-invasive method to identify patients requiring mammography to confirm HMG. | pubmed_617_2363 |
pubmed_617_22800 | We evaluated white bass ovum fatty acid composition as well as embryonic and larval survival after varying n-3 and n-6 long-chain polyunsaturated fatty acid (LC-PUFA) concentrations in maternal diets. Diets containing graded levels (0, 33, 66, or 100%) of squid to menhaden oils were fed daily to apparent satiation to female white bass for 8 weeks prior to spawning. Embryonic survival was negatively related to maternal squid oil intake (P=0.015, R2=0.970). Squid oil-fed broodstock produced ova with decreased 20:5n-3 and increased C18 polyunsaturated fatty acid concentrations, largely reflecting the fatty acid profile of squid oil. Within ovum phospholipid, accumulation of 18:2n-6 may have altered biological function resulting in the lower embryonic survival among ova produced from the squid oil-fed broodstock. Our data suggest the importance of feeding white bass broodstock diets high in total n-3 LC-PUFA (at least 4.0% dry matter), and 20:5n-3-rich lipid sources such as menhaden oil can be effectively utilized by female white bass to produce quality ova. | 10.1007/s10695-009-9376-9 |
pubmed_367_8422 | Mitogen activated protein kinase (MAPK) signaling modules that incorporate AtMPK3 and AtMPK6 control critical aspects of Arabidopsis biology including stress responses, development, cell division and cell death. Arabidopsis stomatal development is negatively regulated by the YDA-MKK4/5-MPK3/6 MAPK module and follows a three step pathway of asymmetric and symmetric divisions followed by terminal differentiation. We have identified the bHLH transcription factor SPCH, which controls entry into the stomatal lineage as a substrate of AtMPK3 and AtMPK6. These findings suggest that SPCH activity may be directly affected by environmental conditions to enable the plant to modify stomatal development in response to suboptimal climates. | pubmed_367_8422 |
pubmed_530_12172 | Charged intermediates and reagents are ubiquitous in organic transformations. The interaction of these ionic species with chiral neutral, anionic, or cationic small molecules has emerged as a powerful strategy for catalytic, enantioselective synthesis. This review describes developments in the burgeoning field of asymmetric ion-pairing catalysis with an emphasis on the insights that have been gleaned into the structural and mechanistic features that contribute to high asymmetric induction. | 10.1002/anie.201205449 |
pubmed_427_1226 | Rats were injected sarcolysin-H3 in a dose of 200 or 500 mC per rat. In animals sacrificed 30, 60 and 90 minutes following sarcolysin-H3 injection an increased radioactivity of DNA was noted that indicates binding of sarcolysin-H3 or its labelled derivatives to DNA. Guanine or quanosine-2', 3' monophosphate injected in animals decreased binding of sarcolysin-H3 to the rat liver DNA (maximum reduction of DNA radioactivity in 47%). In the experiments in vitro guanosine-2', 3' phosphate inhibited sarcolysin-H3 binding to DNA isolated from E. coli. A protective effect of quanine and guanosine-2', 3' phosphate with respect to DNA alkylation seems to be considerably conditioned by a competitive action of these nucleophils. | pubmed_427_1226 |
pubmed_154_16733 | Immunological and epidemiological evidence suggests that the development of natural immunity to meningococcal disease results from colonization of the nasopharynx by commensal Neisseria spp., particularly with N. lactamica. We report here that immunization with N. lactamica killed whole cells, outer membrane vesicles, or outer membrane protein (OMP) pools and protected mice against lethal challenge by a number of diverse serogroup B and C meningococcal isolates in a model of bacteremic infection. Sera raised to N. lactamica killed whole cells, OMPs, or protein pools were found to cross-react with meningococcal isolates of a diverse range of genotypes and phenotypes. The results confirm the potential of N. lactamica to form the basis of a vaccine against meningococcal disease. | 10.1128/IAI.70.7.3621-3626.2002 |
pubmed_564_10462 | Yeast infections play an important role in diabetics. Therefore poorly controlled diabetics and diabetics who have high levels of serum glucose carry a high risk. In the present study, 52 diabetics aged between 17-75 years old have been investigated by means of the incidence of oral candida and have been compared with control group of 33 healthy individuals. In poorly controlled diabetics, the rate of candida growth found high. It is also observed that this ratio is higher in type I than type II, and candida growth rate increased as well as serum glucose level. All of these results are found to be statistically important. | pubmed_564_10462 |
pubmed_11_8992 | OBJECTIVE
To evaluate complication, rate of residual, and tumor recurrence in high-risk location compared to non-high-risk location in hepatocellular carcinoma patients.
MATERIAL AND METHOD
Radiofrequency ablation was performed on 409 tumors in Siriraj Hospital between October 2009 and May 2012. Eighty-eight nodules in 78 atients were treated by RF ablation, which divided into high risk and non-high-risk location. Complete ablation rate, residual tumor recurrent tumor, and complication were retrospectively reviewed.
RESULTS
HCC nodules were in non-high-risk location 34 nodules (38.6%) and in high-risk location 54 nodules (61.4%). Complete tumor ablations were done in 34 nodules (100%) of non-high-risk location group and 50 nodules (92.6%) of high-risk location group. All residual tumors were four nodules (7.2%), which located in subcapsular location. Recurrent tumors were found in six nodules (6.8%), and mean time to recurrence were 210.2 days. Early complication was 10.2% and late complication was 4.5%. The recurrent tumor and complication were not significantly different between two groups.
CONCLUSION
Radiofrequency ablation is effective treatment of hepatocellular carcinoma in high-risk location tumor There is no significant difference in complication and tumor recurrent rate between high-risk and non-high-risk group. However incidence of residual tumor is significantly increased in subcapsular location tumor | pubmed_11_8992 |
pubmed_692_25544 | The hypocretin/orexin (HCRT) system has been associated with both positive and negative drug reinforcement, implicating HCRT receptor 1 (HCRT-R1) signaling in drug-related behaviors for all major drug classes, including opioids. However, to date there are limited studies investigating the role of HCRT receptor 2 (HCRT-R2) signaling in compulsive-like drug seeking. Escalation of drug intake with extended access has been suggested to model the transition from controlled drug use to compulsive-like drug seeking/taking. The current study examined the effects of a HCRT-R2 antagonist, NBI-80713, on heroin self-administration in rats allowed short- (1 h; ShA) or long- (12 h; LgA) access to intravenous heroin self-administration. Results indicate that systemically administered NBI-80713 dose-dependently decreased heroin self-administration in LgA, but not in ShA, animals. Quantitative PCR analyses showed an increase in Hcrtr2 mRNA levels in the central amygdala, a stress-related brain region, of LgA rats. These observations suggest a functional role for HCRT-R2 signaling in compulsive-like heroin self-administration associated with extended access and indicate HCRT-R2 antagonism as a potential pharmacological target for the treatment of heroin dependence. | 10.1038/npp.2014.293 |
pubmed_196_5783 | Patients with chronic obstructive pulmonary disease (COPD) show systemic consequences, such as chronic systemic inflammation leading to changes in the airway, airway penetrability, and endothelial function. Endothelial dysfunction is characterized by a list of alterations of endothelium towards reduced vasodilation, proinflammatory state, detachment and apoptosis of endothelial cells, and development of atherosclerosis. COPD-induced endothelial dysfunction is associated with elevated cardiovascular risk. The increment of physical activities such as pulmonary rehabilitation (PR) training have a significant effect on COPD, thus, PR can be an integrative part of COPD treatment. In this narrative review the focus is on the function of endothelial inflammatory mediators [cytokines, chemokines, and cellular proteases] and pulmonary endothelial cells and endothelial dysfunction in COPD as well as the effects of dysfunction of the endothelium may play in COPD-related pulmonary hypertension. The relationship between smoking and endothelial dysfunction is also discussed. The connection between different pulmonary rehabilitation programs, arterial stiffness and pulse wave velocity (PWV) is presented. Endothelial dysfunction is a significant prognostic factor of COPD, which can be characterized by PWV. We discuss future considerations, like training programs, as an important part of the treatment that has a favorable impact on the endothelial function. | 10.3390/ijms20184329 |
pubmed_28_25231 | Midwifery associations have an important role in several subjects such as professionalisation, developing neonatal health, reducing maternal-fetal mortality, planning labor, professional recognition, planning legislative regulations, developing the profession, and offering quality birth services. The purpose of this study is to explain the contributions of well-known midwifery associations in the world, and in particular in Turkey, to the professional development of midwifery, as well as similarities of midwifery associations in Turkey with other associations, including the position of Turkey in associationalism. The associations have enabled the profession of midwifery to progress, gain autonomy, be legally protected and become more professional. In order for the associations in Turkey to operate effectively, it is recommended that their membership is increased so as to represent more midwives and thus gain more political power and to advance evidence-based applications in midwifery care. | 10.18332/ejm/122388 |
pubmed_738_9893 | INTRODUCTION
Acute pancreatitis (AP) is a healthcare challenge with considerable mortality. Treatment is limited to supportive care, highlighting the need to investigate disease drivers and prognostic markers. Activin A is an established mediator of inflammatory responses, and its serum levels correlate with AP severity. We hypothesized that activin A is independent of body mass index (BMI) and is a targetable promoter of the AP inflammatory response.
METHODS
We assessed whether BMI and serum activin A levels are independent markers to determine disease severity in a cohort of patients with AP. To evaluate activin A inhibition as a therapeutic, we used a cerulein-induced murine model of AP and treated mice with activin A-specific neutralizing antibody or immunoglobulin G control, both before and during the development of AP. We measured the production and release of activin A by pancreas and macrophage cell lines and observed the activation of macrophages after activin A treatment.
RESULTS
BMI and activin A independently predicted severe AP in patients. Inhibiting activin A in AP mice reduced disease severity and local immune cell infiltration. Inflammatory stimulation led to activin A production and release by pancreas cells but not by macrophages. Macrophages were activated by activin A, suggesting activin A might promote inflammation in the pancreas in response to injury.
DISCUSSION
Activin A provides a promising therapeutic target to interrupt the cycle of inflammation and tissue damage in AP progression. Moreover, assessing activin A and BMI in patients on hospital admission could provide important predictive measures for screening patients likely to develop severe disease. | 10.14309/ctg.0000000000000152 |
pubmed_527_112 | The purpose of this work is to develop poly(vinyl alcohol) (PVA) hydrogels incorporating large amounts of beta-cyclodextrin (beta-CD) in order to improve ocular drug loading and to sustain drug release. First, the mono-methacrylated-beta-CD monomer (MA-beta-CD) and the methacrylated-PVA macromer (PVAMA), with a substitution degree of 7%, are synthesized and characterized. Then, the poly(methacrylated-PVA-co-mono-methacrylated-beta-cyclodextrin) (pPVA-beta-CD) hydrogels are prepared by UV-induced polymerization of MA-beta-CD and PVAMA. The highest amount of beta-CD incorporated into the hydrogels is 30 wt%. The hydrogels are further characterized by transmittance, FT-IR, equilibrium swelling ratio (ESR), tensile tests and protein deposition. The results show that pPVA-beta-CD hydrogels possess good transmittance, while the incorporation of beta-CD in the hydrogels improves the tensile strength and decreases the ESR and protein deposition. Finally, puerarin and acetazolamide are used as models to evaluate the drug loading and in vitro release behavior of the pPVA-beta-CD hydrogels. The results indicate that the amount of drug loaded into the pPVA-beta-CD hydrogels progressively increases, while the release rate decreases with increasing beta-CD content. In particular, incorporation of beta-CD efficiently decreases the initial burst release of acetazolamide, while the release, which is almost linear, is sustained for 15 days. The pPVA-beta-CD hydrogels have potential applications as biomedical devices for sustained release of ocular drugs. | 10.1163/156856209X463690 |
pubmed_204_3001 | BACKGROUND
Advance care planning (ACP) is critical to ensure better quality end of life care, and older adults are often a target of ACP. However, ACP interventions and their outcomes are neither standardised nor conclusive.
OBJECTIVES
To synthesise existing ACP systematic reviews and identify the types and outcomes of ACP interventions for older adults in community-based settings.
METHODS
An umbrella review of systematic reviews. The Joanna Briggs Institute Reviewer's Manual was followed. Relevant systematic reviews were searched by utilising bibliographic databases, grey literature sources, and manual searches between April and July, 2019. Nine systematic reviews met the inclusion criteria. Critical appraisal on the selected reviews was conducted. Data were independently extracted using a data extraction tool by two researchers and synthesised based on consensus.
RESULTS
The systematic reviews suggest the critical features of ACP interventions for older adults in community-based settings including clinicians' face-to-face communication with patients and their family members, comprehensive and individualized decisional aids, a proper intensity of ACP interventions, and professional training. When categorising ACP outcomes according to Sudore et al.'s (Journal of Pain and Symptom Management, 55, 2018, 245) framework, action outcomes (e.g., documentation, discussion) were frequently measured with positive outcomes. Quality of care outcomes such as congruence with care preference and healthcare outcomes such as health status were not reported sufficiently.
CONCLUSIONS
The reviews suggested essential features of ACP interventions, which were often omitted in ACP interventions for older adults. Although the outcomes were generally positive, it is inconclusive as to whether ACP interventions eventually improved quality of end of life care or health status of older adults in community-based settings.
IMPLICATIONS FOR PRACTICE
For ACP interventions to be effective and comparable in their outcomes, we recommend adopting the key intervention components identified in this study. As the effects of ACP interventions are inconclusive, further investigations are warranted. | 10.1111/opn.12397 |
pubmed_216_21119 | The Environmental Laboratories Automation Software System or PALMA (Spanish abbreviation) was developed by a multidisciplinary team in order to support the main tasks of heterogeneous air quality control networks. The software process for PALMA development, which can be perfectly applied to similar multidisciplinary projects, was (a) well-defined, (b) arranged between environmental technicians and informatics, (c) based on quality guides, and (d) clearly user-centred. Moreover, it introduces some interesting advantages with regard to the classical step-by-step approaches. PALMA is a web-based system that allows 'off-line' and automated telematic data acquisition from distributed inmission stations belonging not only to homogeneous but also to heterogeneous air quality control networks. It provides graphic and tabular representations for a comprehensive and centralised analysis of acquired data, and considers the daily work that is associated with such networks: validation of the acquired data, alerts with regard to (periodical) tasks (e.g., analysers verification), downloading of files with environmental information (e.g., dust forecasts), etc. The implantation of PALMA has provided qualitative and quantitative improvements in the work performed by the people in charge of the considered control network. | 10.1007/s10661-006-9567-0 |
pubmed_913_7782 | The purification and characterization of three pancreatic trypsinogens A1, A2, and A3, from the African lungfish, Protopterus aethiopicus, is reported. These zymogens are activated by trypsin, by enterokinase, by an acid protease from Aspergillus oryzae, and by autoactivation. The three trypsinogens contain the same amino-terminal amino acid sequence, beginning with the activation peptide Leu-Pro-Leu-Glu-Asp-Asp-Lys-. Like the activation peptide of the previously characterized trypsinogen B [Reeck, G. R., & Neurath, H. (1972) Biochemistry 11, 503] of the same organism, it lacks the tetraaspartyl sequence characteristic of other vertebrate trypsinogens. Two of the corresponding lungfish trypsins were found to have identical amino-terminal sequences for at least 27 residues. These data suggest that the three enzymes are allelic variants. In contrast, the amino acid sequences differ sufficiently from that of trypsinogen B of the same organism to indicate that trypsinogens A and B are the products of different gene loci. | 10.1021/bi00639a015 |
pubmed_755_5164 | The distribution of fibronectin (FN) in the healthy, inflamed and hyperplastic human gingiva was investigated by indirect immunofluorescence. FN appeared as a fibrillar structure in the lamina propria of the healthy gingivae. In the inflamed specimens, FN demonstrated parallel fibres, especially in the coronal areas of the tissue. In the phenytoin gingival overgrowth, tissue FN was observed as thin fibres with variable length. The thin fibres gave the appearance of penetrating the basement membrane of the epithelium. Cyclosporin A gingival enlargement could be differentiated by phenytoin lesions because of the higher length and the parallel distribution of the FN. Finally, FN was observed in the nifedipine gingival overgrowth, where a microfibrillar delicate network gave the appearance of a "cloud"-pattern of distribution. In all of the specimens, blood vessels and nerves could not be stained. These findings show that FN distribution could differentiate the structure of the gingival lesions. | 10.1111/j.1600-0714.1992.tb01006.x |
pubmed_540_575 | Background
The consequences of low levels of environmental heavy metal exposure, as found widely in the United States, in those with impaired renal function remain underexplored.
Methods
We examined the cross-sectional association of indices of renal function with lead and cadmium levels in blood and urine among National Health and Nutrition Examination Survey (NHANES) participants. We used the 1999-2002 cycle, which included measures of cystatin C, in order to quantify renal function most precisely and defined chronic kidney disease (CKD) as an estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2.
Results
In weighted and adjusted analyses of 5638 participants, lead levels were 0.23 (95% CI, 0.03 to 0.42) μg/dl higher among participants with CKD, and 0.05 (95% CI, 0.01 to 0.09) μg/dL higher per 10 ml/min per 1.73 m2 lower eGFR. Cadmium levels were 0.02 (95% CI, 0.01 to 0.03) μg/L higher per 10 ml/min per 1.73 m2 lower eGFR. Black race significantly modified the association of lower eGFR with higher circulating lead levels (P interaction <0.001). A 10 ml/min per 1.73 m2 lower eGFR was associated with a 0.13 (95% CI, 0.06 to 0.21) μg/dl higher lead level among Black participants compared with 0.03 (95% CI, -0.04 to 0.11) μg/dl higher level among White participants. Among the 1852 participants with urinary metal measurements, despite higher circulating levels, those with CKD had significantly lower urinary lead levels (-0.16 [95% CI, -0.30 to -0.01] ng/ml) and urinary lead/creatinine ratios (-0.003 [95% CI, -0.004 to -0.001]).
Conclusions
CKD is associated with higher blood lead levels, particularly among Blacks, and simultaneously, lower urinary lead levels, consistent with the hypothesis that CKD confers a state of heighted susceptibility to heavy metal environmental exposure by reducing its elimination. Given that low levels of exposure remain highly prevalent in the United States, further efforts to protect patients with CKD from heavy metal toxicity may be warranted. | 10.34067/KID.0006782021 |
pubmed_714_19613 | OBJECTIVE
The aim of this study was to assess the role of first-line chemotherapy with paclitaxel and platinum in the treatment of advanced or recurrent cervix cancer.
METHODS
Twenty patients with advanced or recurrent cancer of the cervix with no prior chemotherapy and measurable disease were entered in a phase II trial from September 1995 to September 1998. Seventeen patients were treated with paclitaxel at 135 mg/m(2) over 24 h followed by cisplatin at 75 mg/m(2) every 4 weeks. Three patients with impaired renal function were treated with paclitaxel at 135 mg/m(2) over 3 h with carboplatin at 300 mg/m(2).
RESULTS
A clinical response rate of 45% was noted (two complete responses and seven partial responses) with a median duration of 6 months (range: 1.5-9). The median progression-free interval and overall survival in patients with a clinical response was 10.5 and 13 months, respectively, compared to 4 (P = 0.015) and 6 months in the nonresponders (P = 0. 14). Seven of nine patients (77.8%) with a clinical response are alive. Patients with recurrences outside the radiation field had twice the response rate (60%) than that of those within the radiated field. The chemotherapy was well tolerated; the most significant toxicity was grade 3/4 neutropenia (55%). No patient had discontinuation of chemotherapy due to toxicity.
CONCLUSIONS
First-line chemotherapy with paclitaxel and platinum for advanced and recurrent cervix cancer is promising and deserves consideration for large phase III trials. | 10.1006/gyno.1999.5586 |
pubmed_776_7981 | We report benign retroperitoneal fibrosis associated with renal cell carcinoma in a 56-year-old woman. Based on the preoperative evaluation and initial surgical exploration, the retroperitoneal mass was assumed to be metastatic renal cell carcinoma and chemotherapy rather than surgical resection was offered to the patient. A second opinion was sought and repeat exploration revealed a resectable cell carcinoma and retroperitoneal tissue that was pathologically benign idiopathic retroperitoneal fibrosis. This report emphasizes that a patient with an otherwise resectable primary tumor must undergo multiple, deep biopsies of retroperitoneal masses before making a presumptive diagnosis of malignant retroperitoneal fibrosis secondary to metastatic cancer. | 10.1016/s0022-5347(17)36439-x |
pubmed_363_14243 | Maintenance of Kaposi's sarcoma-associated herpesvirus (KSHV) latent infection depends on the viral episomes in the nucleus being distributed to daughter cells following cell division. The latency-associated nuclear antigen (LANA) is constitutively expressed in all KSHV-infected cells. LANA binds sequences in the terminal repeat regions of the KSHV genome and tethers the viral episomes to chromosomes. To better understand the mechanism of chromosomal tethering, we performed glutathione S-transferase (GST) affinity and yeast two-hybrid assays to identify LANA-interacting proteins with known chromosomal association. Two of the interactors were the methyl CpG binding protein MeCP2 and the 43-kDa protein DEK. The interactions of MeCP2 and DEK with LANA were confirmed by coimmunoprecipitation. The MeCP2-interacting domain was mapped to the previously described chromatin binding site in the N terminus of LANA, while the DEK-interacting domain mapped to LANA amino acids 986 to 1043 in the C terminus. LANA was unable to associate with mouse chromosomes in chromosome spreads of transfected NIH 3T3 cells. However, LANA was capable of targeting to mouse chromosomes in the presence of human MeCP2 or DEK. The data indicate that LANA is tethered to chromosomes through two independent chromatin binding domains that interact with different protein partners. | 10.1128/jvi.76.22.11596-11604.2002 |
pubmed_156_22590 | The role of the DNA phosphodiester backbone in the transfer of melting cooperativity between two helical domains was experimentally addressed with a helix-bulge-helix DNA model, in which the bulge consisted of a varying number of either conformationally flexible propanediol or conformationally constrained bicyclic anucleosidic phosphodiester backbone units. We found that structural communication between two double helical domains is transferred along the DNA backbone over the equivalent of ca. 12-20 backbone units, depending on whether there is a symmetric or asymmetric distribution of the anucleosidic units on both strands. We observed that extension of anucleosidic units on one strand only suffices to disrupt cooperativity transfer in a similar way as if extension occurs on both strands, indicating that the length of the longest anucleosidic inset determines cooperativity transfer. Furthermore, conformational rigidity of the sugar unit increases the distance of coopertivity transfer along the phosphodiester backbone. This is especially the case when the units are asymmetrically distributed in both strands. | 10.1021/ja035313j |
pubmed_530_5108 | Using fluorescence in situ hybridization (FISH) analysis, we examined the replication mode of the centromere region (homologous counterpart) and the aneuploidy level of chromosome 17 in the interphase nuclei of phytohaemagglutinin (PHA)-stimulated peripheral blood lymphocytes from (1) patients with hepatocellular carcinoma (HCC); (2) patients with liver cirrhosis (LC) due to hepatitis C viral infection who are individuals at a higher increased risk for HCC; and (3) healthy control participants. We also compared the allelic-replication asynchrony and aneuploidy frequencies with serum alpha-fetoprotein (AFP) levels. We found a significant increase in centromeric replication asynchrony accompanied by a high frequency of aneuploidy in lymphocytes of HCC patients compared with those of LC patients and healthy control participants. These changes are similar to those previously observed in other types of malignancy (hematological, ovarian, prostate, and breast cancer). The cytogenetic alterations of aneuploidy and strong asynchronous replication displayed in the lymphocytes of HCC patients arose from malignancy, as they were associated neither with an increased risk for cancer nor with an infection. The cytogenetic cancer-associated markers observed in patients' lymphocytes appeared to be superior to serum AFP, the marker currently used for HCC. Thus, the cytogenetic cancer-associated markers may be potentially useful in noninvasive cancer detection. | pubmed_530_5108 |
pubmed_132_630 | Increased exposure to fluorine-containing compounds leads to accumulation of fluorides in hard tissues of bones and teeth, which may result in numerous skeletal and dental disorders. This study evaluates the influence of methionine and vitamin E on fluoride concentration in bones and teeth of rats subjected to long-term exposure to sodium fluoride in drinking water. The study was conducted in 30 3-month-old female Wistar FL rats. The animals were divided into five groups, six rats per group. The control group consisted of rats receiving only distilled water as drinking water. All other groups received NaF in the amount of 10 mg/kg of body mass/day in their drinking water. In addition, respective animal groups received: NaF + Met group--10 mg of methionine/kg of body mass/day, NaF + Met + E group--10 mg of methionine/kg of body mass/day and 3 mg of vitamin E (tocopheroli acetas)/rat/day and NaF + E group--3 mg of vitamin E/rat/day. Femoral bones and incisor teeth were collected for the study, and the fluoride concentration was determined using a fluoride ion-selective electrode. Fluoride concentration in both bones and teeth was found to be higher in the NaF and NaF + Met groups compared to the control group. In groups NaF + Met + E and NaF + E, the study material contained much lower fluoride concentration compared to the NaF group, while the effect was more prominent in the NaF + E group. The results of the studies indicate that methionine and vitamin E have opposite effects on accumulation of fluorides in hard tissue in rats. By stimulating fluoride accumulation, methionine reduces the adverse effect of fluorides on soft tissue, while vitamin E, which prevents excessive accumulation of fluorides in bones and teeth, protects these tissues from fluorosis. Therefore, it seems that combined application of both compounds would be optimal for the prevention of the adverse effects of chronic fluoride intoxication. | 10.1007/s12011-011-9251-2 |
pubmed_549_1676 | Inhibition of Hsp90 has emerged as a therapeutic strategy to target NSCLC subtypes, which are refractory to epidermal growth factor receptor (EGFR) inhibitor-based treatment. We report on a novel small molecule inhibitor of Hsp90, SNX-2112, and an orally bioavailable prodrug analog, SNX-5422. In cellular models of wild-type or mutant EGFR (L858R and T790M mutations), SNX-2112 alone and in combination with erlotinib inhibited EGF activation of pAKT(473) and pSTAT3(705). pERK1/2 and pS6 were also potently inhibited by similar treatments. SNX-2112 reduced EGF cross-talk and activation of the c-Met receptor by causing c-Met degradation. In NCI-H1975 xenograft models, SNX-5422 showed activity as a single agent and in combination with erlotinib resulted in prolonged animal survival at reduced compound concentrations relative to either compound alone. These results support the advanced evaluation of SNX-5422 as a treatment for non-small cell lung cancer (NSCLC), especially in cases where the cancer is driven by c-Met amplification or mutated EGFR forms that are resistant to EGFR inhibitors. | 10.3727/096504009x12596189659240 |
pubmed_408_6691 | 112 patients (78 hypertensives and 34 normotensives) received guidance from a specially trained dietitian on a low-calorie diet. During a mean control period of 10.8 months with a comparable number of visits in each group, the following results were observed: 51% (n = 40) of hypertensive patients achieved a significant weight reduction. In 28% (n = 22) antihypertensive medication was constant and in 23% (n = 18) this medication was reduced or withdrawn. 37% (n = 29) showed no significant changes in body weight or blood pressure and 12% (n = 9) dropped out. In 22 patients a weight reduction of 8.5 kg with a significant fall in blood pressure from 156/99 to 137/90 mm Hg was observed. In 18 hypertensives a weight reduction of 8.5 kg allowed reduction or withdrawal of antihypertensive medication with blood pressure remaining unchanged (139/91 vs. 135/90 mm Hg). Similar results were achieved in 34 normotensive obese patients: 59% (n = 20) had significant weight reduction, 32% (n = 11) no significant reduction in weight or blood pressure, and 9% (n = 3) dropped out. 20 patients with a reduction of 9 kg showed a significant fall in blood pressure from 132/84 to 123/80 mm Hg. The results demonstrate the favourable effect of weight reduction on blood pressure. The time-consuming nature of the frequent and intensive checks should, however, be borne in mind. | pubmed_408_6691 |
pubmed_992_21009 | This study concerns the expression of biomarkers involved in diverse pathways, such as progression, DNA repair mechanisms and angiogenesis to establish an immunoprofile capable of characterizing sporadic versus familial breast cancers (BCs). The aim was to identify a patient subgroup with a different clinical outcome, which could then be directed towards new targeted therapies. Hierarchical cluster analysis (HCA) was carried out using the immunohistochemical score from tissue microarray sections of an initial cohort of 183 (88 sporadic and 95 familial) patients with invasive BC. For the survival analysis, only those patients with complete follow-up were considered. The HCA revealed a 16-protein immunoprofile, nine of which represent the core, as was also found when familial and sporadic BCs were analysed individually. The 16-biomarker immunoprofile was able to identify a group of patients (Group 1) with a more aggressive tumour phenotype. Survival analyses showed that VEGF+ /TWIST1- patients with familial BC of Group 1 tended to demonstrate a lower DFS than the VEGF- /TWIST1+ sporadic BC patients of Group 2 (p = 0.052). Moreover, the entire cohort of VEGF+ /TWIST1- patients showed a statistically worse DFS than the patients with VEGF- /TWIST1+ expression (p = 0.034). In conclusion, we found that tumour stratification based on an immunoprofile is useful to predict the patient clinical behaviour. In particular, our study indicates that the clustering of tumors on the basis of this immunoprofile suggests the possibility to differentiate familial from sporadic BCs and to clinically select those patients who are more likely to benefit from inhibition of the VEGF pathway. | 10.1002/ijc.30868 |
pubmed_769_12122 | OBJECTIVE
To evaluate the clinical features and outcomes of patients who were admitted with a diagnosis of coronavirus disease 2019 (COVID-19) but who were not confirmed with polymerase chain reaction (PCR) positivity.
MATERIAL AND METHODS
This is a retrospective analysis of all patients admitted to two tertiary care centers between March 15 and May 15, 2020, with a diagnosis of COVID-19. From a common database prepared for COVID-19, we retrieved the relevant data and compared the clinical findings and outcomes of PCR-positive patients with those of PCR-negative cases who had been diagnosed on the basis of typical clinical and radiographic findings.
RESULTS
A total of 349 patients were included in the analysis, of which 126 (36.1%) were PCR-negative. PCR-negative patients were younger (54.6 ± 20.8 vs. 60.8 ± 18.9 years, P = .009) but were similar to PCR-positive patients in terms of demographics, comorbidities, and presenting symptoms. They had higher lymphocyte counts (1519 ± 868 vs. 1331 ± 737/mm3, P = .02) and less frequently presented with bilateral radiographic findings (68.3% vs. 79.4%, P = .046) than PCR-positive patients. Besides, they had less severe disease and better clinical outcomes regarding admission to the intensive care unit (9.6% vs. 20.6%, P = .023), oxygen therapy (21.4% vs. 43.5%, P < .001), ventilatory support (3.2% vs. 11.2%, P = .03) and length of hospital stay (5.0 ± 5.0 vs. 9.7 ± 5.9 days, P < .001).
CONCLUSION
This study confirms that about one-third of the COVID-19 patients are PCR-negative and diagnosed based on clinical and radiographic findings. These patients have a more favorable clinical course, shorter hospital stays, and are less frequently admitted to the intensive care unit. | 10.5152/TurkThoracJ.2021.20284 |
pubmed_344_9133 | OBJECTIVE
To evaluate the therapeutic effects and safety of a combination therapy of leflunomide (LEF) and prednisone for the treatment of immunoglobulin A (IgA) nephropathy manifesting with nephrotic syndrome.
METHODS
40 patients with IgA nephropathy manifesting with nephrotic syndrome were randomly divided into two groups. The treatment group was administered with a combination therapy of prednisone and LEF, and the control group with a combination therapy of prednisone and MMF. For the following comparison 24-h urinary protein excretion and the serum levels of albumin, cholesterol, and creatinine before and after the therapy were assessed.
RESULTS
In the treatment group, the medication was markedly effective in 5 cases and effective in 7 cases; the total efficacy rate was 60.0%. In the control group, the treatment was markedly effective in 5 cases and effective in 8 cases; the total efficacy rate was 65.0%. The IgA levels in both groups decreased after therapy. There were no significant differences between the results for the two groups (p > 0.05). The treatments were well tolerated in both groups.
CONCLUSION
LEF is a safe and effective drug for the treatment of IgA nephropathy manifesting with nephrotic syndrome. | 10.5414/cpp48509 |
pubmed_528_24035 | Ghrelin, the endogenous ligand for the growth hormone secretagogue receptor type 1a (GHS-R1a), is a 28 amino acid residue with a post-translational octanoyl modification on Ser3. Despite the biomedical interest in this hormone, the fine details of its regulation and the mechanisms controlling its secretion are largely unknown. The present study analyzes the molecular steps involved in the full lysophosphatidic acid (LPA) receptor-mediated activation of the mitogenic extracellular signal-regulated kinase (ERK) pathway and its consequent role as an inhibitor of ghrelin secretion in the gastric adenocarcinoma cell line AGS. ERK1/2 phosphorylation mediated by LPA proceeds via activation of the type 2 LPA receptor, activation of the nonreceptor tyrosine kinase c-Src, and subsequent transactivation of the epidermal growth factor receptor. Furthermore, LPA-induced ERK activation was found to be independent of matrix metalloproteinases; thus, c-Src acted as the scaffold-transactivating epidermal growth factor receptor. Finally, a correlation was observed between the mitogenic effects of LPA and ghrelin secretion in the human gastric adenocarcinoma cell line AGS. These data suggest a possible physiological role of LPA in ghrelin secretion. The relationship found between LPA and ghrelin secretion might explain the low circulating levels of ghrelin observed in obese patients, as a bona fide reflex of the energetic stores. | 10.1111/j.1742-4658.2007.06091.x |
pubmed_445_2816 | The influence of nicotinamide (NA), a highly suitable precursor substrate for NAD synthesis in various tissues, on islet cell responsiveness was determined. After a 30 minute perifusion with this compound, nicotinamide, in a dose-dependent manner, potentiated glucose-induced insulin secretion. Maximal potentiation (approximately 250%) was observed at 20 mM NA and the threshold for potentiation was 3 mM. In the absence of glucose, NA did not affect basal secretion rates. Mannoheptulose blocked the primary stimulant action of glucose and the potentiating effects of NA. NA did not alter the rate of glucose usage by isolated islets. These results further underscore the possible importance of pyridine nucleotides in stimulated secretion. | 10.1055/s-0028-1092763 |
pubmed_192_6339 | We employ a system of cubic colloids with rounded corners to study the close-packed monolayers that form via convective assembly. We show that by controlled solvent evaporation large densely packed monolayers of colloidal cubes are obtained. Using scanning electron microscopy and particle-tracking algorithms, we investigate the local order in detail and show that the obtained monolayers possess their predicted close-packed optimal packings, the Λ0-lattice and the Λ1-lattice, as well as the simple square-lattice and disordered packings. We further show that shape details of the cube corners are important for the final packing symmetry, where the frequency of the Λ1-lattice increases with decreasing roundness of the corners, whereas the frequency of the Λ0-lattice is unaffected. The formation of both optimal packings is found to be a consequence of the out-of-equilibrium formation process, which leads to small shifts in rows of cubes, thereby transforming the Λ1-lattice into the Λ0-lattice. | 10.1021/acs.langmuir.8b04330 |
pubmed_547_11959 | INTRODUCTION
Lung cancer is highly lethal and resistant to most anticancer interventions. Treatment resistance is mediated, in part, by enhanced expression of cell survival proteins that help facilitate tumor progression. Clusterin is a stress-associated cytoprotective protein up-regulated by various apoptotic triggers in many cancers and confers treatment resistance when overexpressed. The objectives in this study were to evaluate clusterin expression levels in human lung cancer tissue, and to test effects of clusterin silencing using antisense oligonucleotides (ASOs) and short interfering double-stranded RNAs (siRNAs) on chemosensitivity in human lung cancer A549 cells.
METHODS
Clusterin immunostaining was evaluated in a tissue microarray of 149 spotted human lung cancers. The effects of clusterin ASO or siRNA treatment on clusterin expression and chemosensitivity to paclitaxel was examined in A549 cells in vitro while the ability of clusterin ASO to chemosensitize in vivo was evaluated in immunocompromised mice bearing A549 tumors.
RESULTS
More than 80% of human non-small cell lung cancers are immunoreactive for clusterin. Clusterin ASO or siRNA decreased clusterin mRNA expression in A549 cells >75% in a dose-dependent, sequence-specific manner, and significantly enhanced chemosensitivity to paclitaxel in vitro. Characteristic apoptotic DNA laddering was observed after combined treatment with ASO plus paclitaxel, but not with either agent alone. In vivo administration of clusterin ASO, compared to mismatch control oligonucleotide, synergistically enhanced the effects of paclitaxel or gemcitibine to significantly delay A549 tumor growth.
CONCLUSION
These findings identify clusterin as a valid therapeutic target in strategies employing novel multimodality therapy for advanced lung cancer. | pubmed_547_11959 |
pubmed_751_16636 | Cachexia is a common manifestation of advanced cancer and frequently contributes to physical disability and mortality. An increased metabolic rate has been suggested to be one of the causes of cancer-induced cachexia, although the mechanisms producing this hypermetabolism remain unclear. The presence and activation of brown adipose tissue, a highly thermogenic tissue, may result in a hypermetabolic state and be partially responsible for weight loss in cancer patients. To investigate this hypothesis, we examined necropsy samples of peri-adrenal tissues using light microscopy to identify the prevalence of brown adipose tissue in 25 cachectic patients who died from cancer and 15 age-matched subjects who died from other illnesses. Brown adipose tissue was observed in 20 of the cancer patients (80%) compared to 2 of the age-matched subjects (13%). Therefore, our preliminary results indicate that a high prevalence of brown adipose tissue is associated with cancer-induced cachexia and may reflect an abnormal mechanism responsible for profound energy expenditure and weight loss. | 10.1007/BF00402783 |
pubmed_780_18729 | Absorption, distribution, metabolism, and excretion studies were conducted in rats and dogs with rofecoxib (VIOXX, MK-0966), a potent and highly selective inhibitor of cyclooxygenase-2 (COX-2). In rats, the nonexponential decay during the terminal phase (4- to 10-h time interval) of rofecoxib plasma concentration versus time curves after i.v. or oral administration of [(14)C]rofecoxib precluded accurate determinations of half-life, AUC(0-infinity) (area under the plasma concentration versus time curve extrapolated to infinity), and hence, bioavailability. After i.v. administration of [(14)C]rofecoxib to dogs, plasma clearance, volume of distribution at steady state, and elimination half-life values of rofecoxib were 3.6 ml/min/kg, 1.0 l/kg, and 2.6 h, respectively. Oral absorption (5 mg/kg) was rapid in both species with C(max) occurring by 0.5 h (rats) and 1.5 h (dogs). Bioavailability in dogs was 26%. Systemic exposure increased with increasing dosage in rats and dogs after i.v. (1, 2, and 4 mg/kg), or oral (2, 5, and 10 mg/kg) administration, except in rats where no additional increase was observed between the 5 and 10 mg/kg doses. Radioactivity distributed rapidly to tissues, with the highest concentrations of the i.v. dose observed in most tissues by 5 min and by 30 min in liver, skin, fat, prostate, and bladder. Excretion occurred primarily by the biliary route in rats and dogs, except after i.v. administration of [(14)C]rofecoxib to dogs, where excretion was divided between biliary and renal routes. Metabolism of rofecoxib was extensive. 5-Hydroxyrofecoxib-O-beta-D-glucuronide was the major metabolite excreted by rats in urine and bile. 5-Hydroxyrofecoxib, rofecoxib-3',4'-dihydrodiol, and 4'-hydroxyrofecoxib sulfate were less abundant, whereas cis- and trans-3,4-dihydro-rofecoxib were minor. Major metabolites in dog were 5-hydroxyrofecoxib-O-beta-D-glucuronide (urine), trans-3, 4-dihydro-rofecoxib (urine), and 5-hydroxyrofecoxib (bile). | pubmed_780_18729 |
pubmed_324_4549 | Newly synthesized ball-type Zn(II) and Mg(II) phthalocyanines containing four 1,1'-binaphthol substituents at peripheral and non-peripheral positions are presented. The structures of the synthesized compounds were characterized by using elemental analysis, UV-vis, FT-IR, (1)H-NMR and mass spectroscopies. The Φ(F) values were 0.33, 0.08, 0.20 and 0.08 for 6-9, respectively. The Φ(T) values were 0.56, 0.85, 0.64 and 0.88 for 6-9, respectively. All the complexes showed reasonably large triplet lifetimes with τ(T) values of 710 (6), 170 (7), 1490 (8) and 380 μs (9) in DMSO. These complexes offer potential as photosensitizers in photodynamic therapy. | 10.1039/c0dt00920b |
pubmed_358_6127 | PURPOSE
To determine whether the use of autologous blood clot seal (ABCS) after biopsy of lung lesions can reduce or prevent pneumothorax.
MATERIALS AND METHODS
The authors evaluated 100 patients (63 men, 37 women; age range, 27-78 years) with pleural (n = 23) or deep (n = 77) lesions. Thirty-eight patients had emphysema. Patients were randomly assigned to one of two groups: those in whom the biopsy track was sealed with autologous blood clot (n = 50) and those who did not receive autologous blood clot (n = 50). Biopsy was performed with computed tomographic (CT) guidance and a 19-gauge coaxial system. The autologous blood clot, which ranged from 0.5 to 4.5 mL, was injected while the sheath was being withdrawn.
RESULTS
Pneumothorax developed in four of the 23 patients (17%) with pleural lesions and 19 of the 77 patients (24%) with deep lesions. Pneumothorax occurred in four of the 45 patients (9%) who had deep lesions and received autologous blood clot and in 15 of the 32 patients (47%) who had deep lesions and did not receive autologous blood clot (P <.001). In patients with emphysema, pneumothorax occurred in three of the 20 patients (15%) who received autologous blood clot and 10 of the 14 (71%) who did not (P <.001). There were seven large pneumothoraces necessitating treatment; all occurred in patients who did not receive autologous blood clot.
CONCLUSION
Plugging of biopsy tracks with ABCS, particularly after biopsy of deep lung lesions, significantly reduced the frequency of pneumothorax-particularly of large pneumothoraces-and, therefore, the need for treatment and the attendant cost. | 10.1148/radiology.216.1.r00jl3293 |
pubmed_774_14808 | Pests not only attack field crops during the growing season, but also damage grains and other food products stored in granaries. Modified or controlled atmospheres (MAs or CAs) with higher or lower concentrations of atmospheric gases, mainly oxygen (O2), carbon dioxide (CO2), ozone (O3), and nitric oxide (NO), provide a cost-effective method to kill target pests and protect stored products. In this review, the most recent discoveries in the field of MAs are discussed, with a focus on pest control as well as current MA technologies. Although MAs have been used for more than 30 years in pest control and play a role in storage pest management, the specific mechanisms by which insects are affected by and adapt to low O2 (hypoxia) and high carbon CO2 (hypercapnia) are not completely understood. Insect tolerance to hypoxia/anoxia and hypercapnia involves a decrease in aerobic metabolism, including decreased NADPH enzyme activity, and subsequently, decreases in glutathione production and catalase, superoxide dismutase, glutathione-S-transferase, and glutathione peroxidase activities, as well as increases in carboxyl esterase and phosphatase activities. In addition, hypoxia induces energy and nutrient production, and in adapted insects, glycolysis and pyruvate carboxylase fluxes are downregulated, accompanied with O2 consumption and acetate production. Consequently, genes encoding various signal transduction pathway components, including epidermal growth factor, insulin, Notch, and Toll/Imd signaling, are downregulated. We review the changes in insect energy and nutrient sources, metabolic enzymes, and molecular pathways in response to modified O2, CO2, NO, and O3 concentrations, as well as the role of MAs in pest control. This knowledge will be useful for applying MAs in combination with temperature control for pest control in stored food products. | 10.3389/fphys.2019.00206 |
pubmed_994_746 | BACKGROUND
Most children do not meet the recommendation for fruit consumption. Apples are the second most commonly consumed fruit in the US; however, no studies have examined the association of total apple products, apples, apple sauce, and 100 % apple juice consumption on diet quality and weight/adiposity in children.
METHODS
The purpose of this study was to examine the association between various apple consumption forms with diet quality and weight/adiposity in a nationally representative sample of children. Participants were children 2-18 years of age (N = 13,339) from the National Health and Nutrition Examination Survey 2003-2010. Intake was determined using a single interview administered 24-h diet recall. Apple product consumption was determined using the cycle-appropriate USDA Food and Nutrient Database for Dietary Studies food codes. Total diet quality and component scores were determined using the Healthy Eating Index-2010 (HEI). Anthropometrics were determined using standard methods. Covariate adjusted linear and logistic regressions were used to compare apple product consumers with non-consumers; sample weights were used. Probability was set at <0.01.
RESULTS
Approximately 26 % of the population (n = 3,482) consumed some form of apple products. Consumers of apple products, whole apples, apple sauce, and 100 % apple juice had higher HEI scores than non-consumers: 50.4 ± 0.4 v 41.9 ± 0.3, 52.5 ± 0.5 v 42.7 ± 0.3, 52.1 ± 0.8 v 47.2 ± 0.4, and 51.4 ± 0.6 v 46.5 ± 0.4, respectively. Apple products and whole apple consumers had lower BMI z-scores than non-consumers: 0.4 ± 0.04 v 0.5 ± 0.03 and 0.3 ± 0.1 v 0.5 ± 0.02, respectively. Apple products and whole apple consumers were 25 % (0.59-0.95 99(th) CI) and 30 % (0.52-0.95 99(th) CI), respectively, were less likely to be obese than non-consumers.
CONCLUSIONS
Consumption of any form of apples contributed to the fruit recommendation of children and improved diet quality. Apples should be included in the diets of children as a component of an overall healthy diet. | 10.1186/s12937-015-0040-1 |
pubmed_968_20350 | Perforation is a known complication of endoscopic resection and has been managed with endoscopic defect closure, antibiotics and close observation. Closure of duodenal perforations are more challenging due to the presence of gastric and pancreaticobiliary secretions. The use of endoluminal vacuum therapy (EVT) to divert flow and aid closure is increasingly prevalent and may avoid high-risk surgery. We describe the use of endoluminal vacuum closure to salvage an iatrogenic duodenal perforation in a 57-year-old male who underwent an endoscopic mucosal resection of a 35-mm polypoid lesion on the posterior wall of the second portion of the duodenum. The endoluminal wound vac successfully controlled leakage and allowed defect closure. EVT is an emerging technique that can effectively manage complicated injuries throughout the GI tract and may allow enhanced recovery by avoiding surgical salvage and its associated morbidity and mortality. | 10.1093/jscr/rjab479 |
pubmed_969_16023 | The bidirectional cavopulmonary shunt improves systemic arterial oxygen saturation without increasing ventricular work or pulmonary vascular resistance. Since 1983, 17 patients have undergone a cavopulmonary shunt procedure (five primary operations, 12 secondary operations). Diagnoses were single ventricle complex (n = 4), hypoplastic right heart syndrome (n = 10), and hypoplastic left ventricle (n = 3). Age at primary operation ranged from 3 1/2 to 30 months (median 6 months). Weight ranged from 3.5 to 9.7 kg. Age at secondary operation ranged from 10 months to 14 years (median 15 months). Seven cavopulmonary shunt operations were performed without cardiopulmonary bypass (six via thoracotomy and one via sternotomy) and 10, with cardiopulmonary bypass. All patients in the bypass group had additional procedures: takedown of modified Blalock-Taussig shunt, seven patients; revision of right ventricular outflow tract, four patients; reconstruction of pulmonary arteries, four patients; tricuspid valvuloplasty, one patient; and Damus procedure, one patient. There was one (1/17) operative death (Damus procedure). One patient required early revision. Follow-up ranges from 1 to 53 months (median 23 months). Twelve of 16 had a good to excellent late result, with a rise in mean arterial oxygen saturation from 69% to 83%. Three patients died late (4 to 53 months) (pulmonary vascular disease, pulmonary arteriovenous malformations, and pneumonia, one patient each). There was one late failure (converted to Glenn shunt). The cavopulmonary shunt is an excellent palliative procedure when right atrium-pulmonary artery connection (modified Fontan) must be deferred because of age, weight, or anatomic considerations. Five patients have undergone right atrium-pulmonary artery connection later. In addition, at the time of the modified Fontan operation, the cavopulmonary shunt approach may optimize the anatomic connection (eight additional patients). | pubmed_969_16023 |
pubmed_481_12365 | Reductive dechlorination of the Aroclor 1260 residue in Woods Pond (Lenox, Mass.) sediment samples was investigated for a year at incubation temperatures from 4 to 66 degrees C. Sediment slurries were incubated anaerobically with and without 2,3,4,6-tetrachlorobiphenyl (2346-CB; 350 microM) as a primer for dechlorination of the Aroclor 1260 residue. Dechlorination of the Aroclor residue occurred only in live samples primed with 2346-CB and only at 8 to 34 degrees C and 50 to 60 degrees C. The extent and pattern of polychlorinated biphenyl (PCB) dechlorination were temperature dependent. At 8 to 34 degrees C, the dechlorination resulted in 28 to 65% decreases of the hexathrough nonachlorobiphenyls and corresponding increases in the tri- and tetrachlorobiphenyls. At 12 to 30 degrees C, 30 to 40% of the hexa- through nonachlorobiphenyls were dechlorinated in just 3 months. The optimal temperature for overall chlorine removal was 20 to 27 degrees C. We observed four different microbial dechlorination processes with different but partially overlapping temperature ranges, i.e., Process N (flanked meta dechlorination) at 8 to 30 degrees C, Process P (flanked para dechlorination) at 12 to 34 degrees C, Process LP (unflanked para dechlorination) at 18 to 30 degrees C, and Process T (a very restricted meta dechlorination of specific hepta- and octachlorobiphenyls) at 50 to 60 degrees C. These temperature ranges should aid in the development of strategies for the enrichment and isolation of the microorganisms responsible for each dechlorination process. The incubation temperature determined the relative dominance of the four PCB dechlorination processes and the extent and products of dechlorination. Hence, understanding the effects of temperature on PCB dechlorination at contaminated sites should assist in predicting the environmental fate of PCBs or planning bioremediation strategies at those sites. | 10.1128/aem.63.12.4818-4825.1997 |
pubmed_0_4379 | Metabolic and immune-related pathways intersect at numerous levels. Their common regulation is effectuated by several hormonal signaling routes that involve specific nuclear hormone receptors and adipokines. Glucocorticoids and leptin are hormones that play a key role in coordinating energy metabolism and food-seeking behavior during energy deficiency as does the nuclear hormone receptor Peroxisome Proliferator Activated Receptor α (PPARalpha). Importantly, the glucocorticoid, leptin, and PPARalpha signaling routes share a profound role in governing inflammation and other immune-related processes. Using specific examples, this chapter aims at illustrating the interplay between metabolism and immunity/inflammation by discussing common endocrine and transcriptional regulators of metabolism and inflammation and by highlighting the interaction between macrophages and metabolically active cells in liver and adipose tissue. Convergence of metabolic and immune signaling is likely at least partially driven by the evolutionary need during times of food insufficiency to minimize loss of energy to processes that are temporarily nonessential to the survival of the species. | 10.1007/978-3-642-14426-4_2 |
pubmed_1073_6961 | DAS181, (study drug, Fludase®) was developed for treatment of influenza and parainfluenza infections. Delivered by inhalation, DAS181 cleaves sialic acid receptors from respiratory epithelial cells. Treatment of influenza for three days with DAS181 reduced viral shedding. To increase deposition in the upper airways and decrease systemic absorption, the particle size was increased to 10μm. We conducted two Phase I trials with three cohorts, randomized 2:1, active drug to placebo. The initial cohort got a single 20mg dose of DAS181, or placebo; the second, 20mg DAS181 or placebo for 10days, and the third got 20mg of DAS181 or placebo for 3days. Formulations differed slightly in their excipients. Subjects in the 1- and 3-day cohorts completed dosing without serious adverse events. Two subjects in the 10-day cohort stopped at Day 9 after developing respiratory and systemic symptoms, and a third experienced a decrease in FEV1 (Forced Expiratory Volume in 1s) after the 9th dose and a further decline after the 10th dose. Plasma DAS181, in the 10-day cohort, peaked and began falling before the last dose. Antibodies, predominately IgG with neutralizing activity, were detected in 15/18 subjects by Day 30. The highest IgG concentrations were in the 10-day cohort. The respiratory adverse events occurring after seven days and rapid drug clearance during continued dosing are consistent with the induction of DAS181 antibodies. This could preclude use of this medication for longer than seven days or for repeated courses. (These studies have been registered at ClinicalTrials.gov under registration Nos. NCT 00527865 and NCT 01651494.). | pubmed_1073_6961 |
pubmed_329_9736 | The pigments, execution technique and repainting used on the polychrome wood ceilings and doors in the Casa de Pilatos (Seville, Spain) were studied using portable X-ray fluorescence equipment. Cross-sections of small samples were also analysed by optical microscopy, SEM with EDX analysis, micro-Raman and micro-infrared spectroscopy and X-ray diffraction. These carpentry works are magnificent examples of the Mudéjar art made in Spain in the early 16th century. Portable X-ray fluorescence gave good information on the different components of the polychrome. The SEM-EDX study of the surfaces of small samples gave information on their components and also characterized the compounds that had been deposited or formed by environmental contamination or by the alteration of some pigments. The SEM-EDX study of cross-sections facilitated the characterization of all layers and pigments from the support to the most external layer. The following pigments were characterized: red (cinnabar/vermillion, lead oxide, iron oxides and orpiment/realgar), black (carbon black), white (white lead and titanium barium white), yellow-orange-red-brown (orpiment/realgar and iron oxides), green (chromium oxide), blue (indigo blue and ultramarine blue), and gilding (gold leaf on bole). False gold, bronze and brass were also found. The pigments were applied with the oil painting technique over a support layer that had been primed with animal glue. This support layer was gypsum in some cases and white lead in others. This study is essential to the polychrome conservation of the studied artwork, and it will help clarify uncertainties in the history and painting of Mudéjar art. | 10.1016/j.saa.2016.09.027 |
pubmed_1100_2287 | The contribution of binocular visual feedback to the kinematics of human prehension was studied in two related experiments. In both experiments, the field of view of each eye was independently controlled by means of goggles fitted with liquid-crystal shutters. While wearing these goggles, which permitted either a binocular or a monocular view of the world, subjects were required to reach out and grasp a target object, which varied in size and position from trial to trial. In experiment 1, two viewing conditions were used. In one condition, binocular vision was available throughout the entire trial; in the second condition, the initial binocular view was replaced by a monocular view after the reaching movement had been initiated. When only monocular feedback was available, subjects showed a prolonged deceleration phase, although the time they spent in contact with the object was the same in both conditions. In experiment 2, monocular vision was available throughout a given trial in one condition and was replaced by binocular vision upon movement initiation in the second condition. Subjects in this experiment also displayed a prolonged deceleration phase in the monocular feedback condition relative to their performance in the binocular feedback condition. Unlike experiment 1, however, allowing only monocular feedback resulted in an increase in the amount of time subjects spent in contact with the object. Moreover, the object contact phases under the two conditions of experiment 2 were much longer than those observed in experiment 1, in which subjects received initial binocular views of the object.(ABSTRACT TRUNCATED AT 250 WORDS) | 10.1007/BF00229116 |
pubmed_1134_2769 | BACKGROUND
Lumbar midline interlaminar and transforaminal (TF) epidural steroid injections are treatments for low back pain with radiculopathy secondary to degenerative disk disease. Since pain generators are located anteriorly in the epidural space, ventral epidural spread is the logical target for placement of antiinflammatory medications. In this randomized, prospective, observational study, we compared contrast flow patterns in the epidural space using the parasagittal interlaminar (PIL) and transforaminal approaches with continual fluoroscopic guidance.
METHODS
Sixty adult patients with low back pain and unilateral radiculopathy from herniated or degenerated discs were enrolled. Subjects were randomly assigned to one of two groups: TF or PIL (30 in each). All procedures were performed using continual fluoroscopic guidance and 5 mL of contrast. Contrast spread was rated (primary outcome measure) by the interventionalist. Spread was scored 0-2, with 0 = no anterior spread; 1 = anterior spread, same level as needle insertion; and 2 = anterior spread at > or = 1 segmental level. The secondary outcome measure was analgesia at 2 wk, 1, 3, and 6 mo.
RESULTS
One hundred percent (29 of 29) patients in the PIL group and 75% (21 of 28) patients in the TF group demonstrated anterior epidural spread. The mean spread grade was 1.93 (95% confidence interval [CI], 1.83-2.0) in the PIL group and 1.46 (95% CI, 1.17-1.46) in the TF group (P = 0.003). Mean fluoroscopy time was 28.96 s (95% CI, 23.9-34.1 s) in the PIL group and 46.25 s (95% CI, 36.27-56.23 s) in the TF group (P = 0.003). Visual analog scale scores were equivalent between groups.
CONCLUSIONS
The PIL approach is superior to the TF approach for placing contrast into the anterior epidural space with reduction in fluoroscopy times and an improved spread grade. With increasing attention to neurological injury associated with TF, the PIL approach may be more suitable for routine use. | 10.1213/ane.0b013e3181605e9b |
pubmed_323_15813 | OBJECTIVE
To investigate the association between kidney dysfunction and haplotypes in sickle cell disease.
METHODS
A cohort of 84 sickle cell disease patients, treated in a public health service in Fortaleza, Brazil, was studied. Hemoglobin S haplotypes were obtained from 57 patients as they had recently received blood transfusions with 18 of them agreeing to undertake urinary concentrating ability and acidification tests. The glomerular filtration rate was estimated using the Modification of Diet in Renal Disease Study equation. Urinary concentration was evaluated utilizing the urinary and serum osmolality ratio (U/Posm) after 12 hours of water deprivation. Urinary acidification was evaluated by measuring the urinary pH before and after the administration of oral CaCl2. The analysis of the haplotypes of the beta S gene cluster was carried out by polymerase chain reaction-restriction fragment length polymorphism. The analysis of variance (ANOVA) test was used for multiple comparisons of means and the Newman-Keuls test was used to identify which groups were significantly different.
RESULTS
The mean age of the patients was 33 ± 13 years with 64.2% being females. The glomerular filtration rate was normal in 25 cases (30%) and a rate > 120 mL/min was seen in 52 cases (62%). Urinary concentration deficit was found in all patients who underwent the test and urinary acidification in 22%. There was no significant difference when comparing patients with the Bantu/Bantu and Benin/Benin haplotypes. On comparing patients with the Central African Republic-haplotype however, a higher number had glomerular filtration rates between 60 and 120 mL/min.
CONCLUSION
There was no significant difference among sickle cell disease patients regarding the haplotypes and kidney dysfunction. | 10.5581/1516-8484.20130052 |
pubmed_297_1799 | Anomalous small-angle X-ray scattering (ASAXS) and resonant soft X-ray scattering (RSoXS) are two related techniques that can enable element-specific structural information to be obtained. The development of iron-fortified milk products can greatly benefit from such techniques, allowing the structure of iron and other minerals (such as native calcium) within the casein micelle to be determined. Each method has advantages and disadvantages: for ASAXS, the sample preparation is straightforward, but the signal is relatively low and information about the structure of Ca is difficult to access. RSoXS can be used to study both Ca and Fe, and the element-specific signals observed are proportionally much higher; however, the measurements are challenging due to the difficulty of precise control of the solution thickness using currently available vacuum-compatible liquid cells. Nevertheless, complementary results from both techniques indicate Fe is co-located with Ca, i.e. within the colloidal calcium phosphate nanoclusters that are present within native casein micelles in milk. | 10.1107/S1600577518007774 |
pubmed_1140_14108 | Experiencing oneself as the cause of an action is a fundamental building block for a sense of self. A recent study by Sato and Yasuda provides evidence that motor prediction contributes to the experience of agency. Their findings demonstrate that agency is experienced not only for intended, but also for erroneous, unintended actions. This extends our knowledge on the phenomenology of action, and raises questions about the relation between explicit reports and agency-related changes in sensation and perception. | 10.1016/j.tics.2005.04.006 |
pubmed_2_11815 | Abuse of the stimulant designer drug methylone (methylenedioxymethcathinone) has been documented in most parts of the world. As with many of the new designer drugs that continuously appear in the illicit drug market, little is known about the pharmacokinetics of methylone. Using in vitro studies, CYP2D6 was determined to be the primary enzyme that metabolizes methylone, with minor contributions from CYP1A2, CYP2B6, and CYP2C19. The major metabolite was identified as dihydroxymethcathinone, and the minor metabolites were N-hydroxy-methylone, nor-methylone, and dihydro-methylone. Measuring the formation of the major metabolite, biphasic Michaelis-Menten kinetic parameters were determined: V(max,1) = 0.046 ± 0.005 (S.E.) nmol/min/mg protein, K(m,1) = 19.0 ± 4.2 μM, V(max,2) = 0.22 ± 0.04 nmol/min/mg protein, and K(m,2) = 1953 ± 761 μM; the low-capacity and high-affinity contribution was assigned to the activity of CYP2D6. Additionally, a time-dependent loss of CYP2D6 activity was observed when the enzyme was preincubated with methylone, reaching a maximum rate of inactivation at high methylone concentrations, indicating that methylone is a mechanism-based inhibitor of CYP2D6. The inactivation parameters were determined to be K(I) = 15.1 ± 3.4 (S.E.) μM and k(inact) = 0.075 ± 0.005 minute(-1). | 10.1124/dmd.112.050880 |
pubmed_1027_11235 | The neurobiology of hair cells is reviewed, including their transduction apparatus, the production and nature of receptor potentials, and the similarities and differences between inner hair cells and outer cells (OHCs). Intracellular recordings from hair cells in vivo are discussed. This is followed by a consideration of effects of OHC lesions and consequent notions about OHC functions. Feedback in the cochlea is then considered, and the role of OHCs as the feedback element is examined, along with putative means of producing the feedback. | pubmed_1027_11235 |
pubmed_821_1709 | CONTEXT
Electroconvulsive therapy (ECT) is highly effective for treatment of major depression, but naturalistic studies show a high rate of relapse after discontinuation of ECT.
OBJECTIVE
To determine the efficacy of continuation pharmacotherapy with nortriptyline hydrochloride or combination nortriptyline and lithium carbonate in preventing post-ECT relapse.
DESIGN
Randomized, double-blind, placebo-controlled trial conducted from 1993 to 1998, stratified by medication resistance or presence of psychotic depression in the index episode.
SETTING
Two university-based hospitals and 1 private psychiatric hospital.
PATIENTS
Of 290 patients with unipolar major depression recruited through clinical referral who completed an open ECT treatment phase, 159 patients met remitter criteria; 84 remitting patients were eligible and agreed to participate in the continuation study.
INTERVENTIONS
Patients were randomly assigned to receive continuation treatment for 24 weeks with placebo (n = 29), nortriptyline (target steady-state level, 75-125 ng/mL) (n = 27), or combination nortriptyline and lithium (target steady-state level, 0.5-0.9 mEq/L) (n = 28).
MAIN OUTCOME MEASURE
Relapse of major depressive episode, compared among the 3 continuation groups.
RESULTS
Nortriptyline-lithium combination therapy had a marked advantage in time to relapse, superior to both placebo and nortriptyline alone. Over the 24-week trial, the relapse rate for placebo was 84% (95% confidence interval [CI], 70%-99%); for nortriptyline, 60% (95% CI, 41%-79%); and for nortriptyline-lithium, 39% (95% CI, 19%-59%). All but 1 instance of relapse with nortriptyline-lithium occurred within 5 weeks of ECT termination, while relapse continued throughout treatment with placebo or nortriptyline alone. Medication-resistant patients, female patients, and those with more severe depressive symptoms following ECT had more rapid relapse.
CONCLUSIONS
Our study indicates that without active treatment, virtually all remitted patients relapse within 6 months of stopping ECT. Monotherapy with nortriptyline has limited efficacy. The combination of nortriptyline and lithium is more effective, but the relapse rate is still high, particularly during the first month of continuation therapy. | 10.1001/jama.285.10.1299 |
pubmed_2_1818 | BACKGROUND
Tuberculosis (TB) is a major public health problem globally. Little is known about TB incidence in adolescents who are a proposed target group for new TB vaccines. We conducted a study to determine the TB incidence rates and risk factors for TB disease in a cohort of school-going adolescents in a high TB burden area in South Africa.
METHODS
We recruited adolescents aged 12 to 18 years from high schools in Worcester, South Africa. Demographic and clinical information was collected, a tuberculin skin test (TST) performed and blood drawn for a QuantiFERON TB Gold assay at baseline. Screening for TB cases occurred at follow up visits and by surveillance of registers at public sector TB clinics over a period of up to 3.8 years after enrolment.
RESULTS
A total of 6,363 adolescents were enrolled (58% of the school population targeted). During follow up, 67 cases of bacteriologically confirmed TB were detected giving an overall incidence rate of 0.45 per 100 person years (95% confidence interval 0.29-0.72). Black or mixed race, maternal education of primary school or less or unknown, a positive baseline QuantiFERON assay and a positive baseline TST were significant predictors of TB disease on adjusted analysis.
CONCLUSION
The adolescent TB incidence found in a high burden setting will help TB vaccine developers plan clinical trials in this population. Latent TB infection and low socio-economic status were predictors of TB disease. | 10.1371/journal.pone.0059652 |
pubmed_1112_19671 | OBJECTIVES
Anaemia is a frequent complication after cardiopulmonary bypass surgery. Iron therapy has been variably employed by medical centres over the years. In our study we test the clinical effectiveness of intravenous and oral iron supplementation in correcting anaemia, and its impact on blood transfusion requirements, in patients undergoing cardiopulmonary bypass surgery.
METHODS
A double-blind, randomized, placebo-controlled clinical trial with three parallel groups of patients. Group I (n = 54): intravenous iron(III)-hydroxide sucrose complex, three doses of 100 mg/24 h during pre- and postoperative hospitalization and 1 pill/24 h of oral placebo in the same period and during 1 month after discharge. Group II (n = 53): oral ferrous fumarate iron 1 pill/24 h pre- and postoperatively and during 1 month after discharge, and intravenous placebo while hospitalized. Group III (n = 52): oral and intravenous placebo pre- and postoperatively, following the same protocol. Data were collected preoperatively, at theatre, at intensive care unit admission, before hospital discharge and 1 month later.
RESULTS
(1) Baseline clinical and demographic characteristics and surgical procedures were similar in the three groups; (2) no inter-group differences were found in haemoglobin and haematocrit during the postoperative period; (3) the intravenous iron group showed higher serum ferritin levels at hospital discharge (1321 ± 495 ng/ml; P < 0.001) and 1 month later (610 ± 387; P < 0.001) compared with the other groups and (4) we did not observe statistical differences in blood transfusion requirements between the three groups.
CONCLUSIONS
The use of intravenous or oral iron supplementation proved ineffective in correcting anaemia after cardiopulmonary bypass and did not reduce blood transfusion requirements. [Current Controlled Trials number: NCT01078818 (oral and intravenous iron in patients postoperative cardiovascular surgery under EC)]. | 10.1093/icvts/ivs344 |
pubmed_316_20341 | The effects of dexfenfluramine on food intake of rats are compared and contrasted among several paradigms. Paradigms that involve overfeeding rather than deprivation, show a greater effect of the agent. Furthermore, both stress-induced eating as well as a food-motivated response (running) are particularly sensitive to inhibition by dexfenfluramine. The results of chronic administration of dexfenfluramine on both behavior and neurochemistry are reviewed, with particular reference to brain 5-HT. The effects of dexfenfluramine on diet selection and conditioned preferences are discussed. Finally, we suggest that species differences may exist in either the neurochemical and/or behavioral responses to dexfenfluramine. | pubmed_316_20341 |
pubmed_563_4161 | Potassium (K+) is indispensable for the regulation of a plethora of functions like plant metabolism, growth, development, and abiotic stress responses. K+ is associated with protein synthesis and entangled in the activation of scores of enzymes, stomatal regulation, and photosynthesis. It has multiple transporters and channels that assist in the uptake, efflux, transport within the cell as well as from soil to different tissues, and the grain filling sites. While it is implicated in ion homeostasis during salt stress, it acts as a modulator of stomatal movements during water deficit conditions. K+ is reported to abate the effects of chilling and photooxidative stresses. K+ has been found to ameliorate effectively the co-occurrence of drought and high-temperature stresses. Nutrient deficiency of K+ makes leaves necrotic, leads to diminished photosynthesis, and decreased assimilate utilization highlighting the role it plays in photosynthesis. Notably, K+ is associated with the detoxification of reactive oxygen species (ROS) when plants are exposed to diverse abiotic stress conditions. It is irrefutable now that K+ reduces the activity of NADPH oxidases and at the same time maintains electron transport activity, which helps in mitigating the oxidative stress. K+ as a macronutrient in plant growth, the role of K+ during abiotic stress and the protein phosphatases involved in K+ transport have been reviewed. This review presents a holistic view of the biological functions of K+, its uptake, translocation, signaling, and the critical roles it plays under abiotic stress conditions, plant growth, and development that are being unraveled in recent times. | 10.1080/02648725.2022.2143317 |
pubmed_100_8427 | Over the last several years the involvement of the innate immune system in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE) has become well established. As systemic sclerosis (SSc; scleroderma) shares clinical features and autoantibodies with SLE, investigation has recently focused on the role of innate immunity in SSc. This has been supported by recent genetic studies. However, unlike SLE and other related autoimmune diseases, SSc patients suffer from pathologic fibrosis of skin and internal organs. The fibrotic component of SSc shares several features with syndromes following environmental exposures to agents such as organic solvents, silica dust and bleomycin. Recent work in SSc and these related fibrotic diseases have identified several areas in which innate immunity can stimulate inflammation as well as fibrosis. This article will focus on the recent discoveries identifying a prominent role of cells of the innate immune system, pattern recognition receptors, and activation of dendritic cells in the pathogenesis of SSc. | 10.1586/eci.11.40 |
pubmed_385_12956 | PURPOSE
To compare the outcome of treatment for myopia by phakic intraocular lens (IOL) implantation or by clear lens extraction (CLE).
SETTING
Service d'Ophtalmologie, Hopital Purpan, Toulouse, France.
METHODS
Thirty-nine patients from 32 to 49 years of age were studied. Forty-one eyes of 21 patients received a phakic IOL, and 36 eyes of 18 patients had phacoemulsification of the crystalline lens. The mean preoperative spherical equivalent (SE) was -13.6 diopters (D) +/- 3.0 (SD) in the phakic IOL group and -16.7 +/- 3.8 D in the CLE group.
RESULTS
Postoperatively, the mean SE was -1.06 +/- 0.78 D in the IOL group and -1.88 +/- 0.83 D in the CLE group. At 12 months, the best corrected visual acuity (BCVA) had improved in 78.0% of eyes in the IOL group and 83.3% in the CLE group; no eye lost 1 line of BCVA. In 3 eyes (7.31%) in the IOL group, opacification of the crystalline lens developed 34, 36, and 44 months after implantation. Visual recovery after phacoemulsification was excellent. No eye in this group lost 1 or more lines of BCVA between 1 and 4 years of the initial surgery. In the CLE group, a retinal detachment occurred in 2 eyes at 39 and 43 months. The final BCVA in these eyes was counting fingers and 20/200.
CONCLUSION
Implantation of a phakic IOL in a highly myopic eye of a patient between 30 and 50 years of age can be considered an adequate technique with a lower risk for loss of BCVA than CLE. | 10.1016/j.jcrs.2004.02.082 |
pubmed_749_15002 | OBJECTIVE
Individuals with serious mental illness endorse many more medical and psychosocial barriers to physical activity (PA) than the general population. However, it is unknown if older adults with serious mental illness are at greater risk of experiencing barriers to PA than their younger counterparts.
METHOD
The present study utilized a national VA dataset to compare veterans with serious mental illness ages 55 and older (n = 9,044) to veterans with serious mental illness ages 54 and younger (n = 8,782) on their responses to a questionnaire assessment of barriers to PA.
RESULTS
Older veterans were more likely to endorse arthritis and cardiopulmonary disease, and less likely to endorse work schedule, as barriers to PA.
CONCLUSIONS AND IMPLICATIONS FOR PRACTICE
Interventions designed to increase PA for young/middle-aged adults with serious mental illness may be broadly useful for older adults with serious mental illness, with some modification to address specific health concerns. (PsycINFO Database Record | 10.1037/prj0000245 |
pubmed_878_3734 | Epithelial cell polarization involves several kinase signaling cascades that eventually divide the surface membrane into an apical and a basolateral part. One kinase, which is activated during the polarization process, is phosphoinositide 3-kinase (PI3K). In MDCK cells, the basolateral potassium channel Kv7.1 requires PI3K activity for surface-expression during the polarization process. Here, we demonstrate that Kv7.1 surface expression requires tonic PI3K activity as PI3K inhibition triggers endocytosis of these channels in polarized MDCK. Pharmacological inhibition of SGK1 gave similar results as PI3K inhibition, whereas overexpression of constitutively active SGK1 overruled it, suggesting that SGK1 is the primary downstream target of PI3K in this process. Furthermore, knockdown of the ubiquitin ligase Nedd4-2 overruled PI3K inhibition, whereas a Nedd4-2 interaction-deficient Kv7.1 mutant was resistant to both PI3K and SGK1 inhibition. Altogether, these data suggest that a PI3K-SGK1 pathway stabilizes Kv7.1 surface expression by inhibiting Nedd4-2-dependent endocytosis and thereby demonstrates that Nedd4-2 is a key regulator of Kv7.1 localization and turnover in epithelial cells. | 10.1074/jbc.M113.525931 |
pubmed_814_12155 | OBJECTIVE
In patients with partial meniscus defect, the implantation of polyurethane meniscal scaffold has become a common method for the treatment of meniscus vascular entry and tissue regeneration. However, it is unclear whether polyurethane meniscal scaffold will yield better clinical and MRI results after surgery. This meta-analysis compared the clinical and MRI results of polyurethane meniscal scaffold in some patients with meniscus defects.
METHODS
By searching PubMed, Embase, and Cochrane Library, a systematic review of studies evaluating the clinical outcomes of patients with polyurethane meniscal scaffold implantation. The search terms used are: "meniscus", "meniscal", "scaffold", "Actifit" "polyurethane" and "implant". The study was evaluated based on the patient's reported outcome score, accompanying surgery, and radiology results. Genovese scale was used to evaluate morphology and signal intensity, and Yulish score was used to evaluate the imaging performance of articular cartilage.
RESULTS
There were 16 studies that met the inclusion criteria, a total of 613 patients, and the overall average follow-up time was 41 months. The clinical scores at the final follow-up, such as VAS, IKDC, Tegner, and KOOS, were significantly improved compared with preoperatively. The MS, SI, and IIRMC scores evaluated in MRI showed no significant difference between preoperative and final follow-up. However, for AC (OR 0.34, 95% CI 0.11-1.00; P = 0.05) and AME (OR 0.08, 95% CI 0.03-0.22; P < 0.01), the final follow-up results were worse than preoperatively.
CONCLUSIONS
This meta-analysis found that compared with preoperative, the clinical effect of the final follow-up was significantly improved. However, MS, SI, and IIRMC in MRI parameters did not change significantly. In addition, the final follow-up results of AC and AME showed a deteriorating trend. Therefore, for patients with partial meniscus defects, polyurethane meniscal scaffold seem to be a viable option, and further research is needed to determine whether the deterioration of AC and AME is clinically relevant. | 10.1016/j.jor.2021.02.027 |
pubmed_183_12007 | OBJECTIVE
To investigate the effectiveness and safety of triptolide-eluting stents implanted in porcine coronary arteries for restenosis prevention, and its effect on the expression of proliferating cell nuclear antigen (PCNA) and P27(kip1).
METHODS
Ten triptolide-eluting stents and 10 stainless steel stents (control) were implanted in 20 porcine coronary arteries at random. Four weeks later, angiography of the arteries was performed along with also histopathological and immunochemical examinations.
RESULTS
The in-stent minimal lumen diameter of triptolide group was significantly greater, and the neointimal area significantly smaller, than those of the control group (P<0.05). PCNA expression was significantly lower while P27(kip1) protein significantly higher in triptolide group than in the control group (P<0.05).
CONCLUSION
Triptolide-eluting stent can effectively inhibit neointimal formation to prevent restenosis in porcine coronary artery 4 weeks after implantation, probably by inhibiting P27(kip1) expression and consequently vascular smooth muscle cell proliferation. | pubmed_183_12007 |
pubmed_431_14847 | Chondroma is a remarkably rare lesion of the oral soft tissues. Most previously reported chondromas of this area have been associated with varying percentages of fibrous, adipose or bone tissues, and the occurrence of such neoplasms exclusively composed of chondromatous tissue is exceedingly rare. We report the clinicopathological features of a pure chondroma of the dorsum of the tongue, occurring in a 51-year-old woman and discuss the possible origin of the tumour. | 10.1111/j.1365-2230.2008.02717.x |
pubmed_538_19469 | Protonation of (N-N)PtPh(2) (1; N-N = diimine ArN=CMe-CMe=NAr with Ar = 2,6-Me(2)C(6)H(3) (a), 2,4,6-Me(3)C(6)H(2) (b), 4-Br-2,6-Me(2)C(6)H(2) (c), 3,5-Me(2)C(6)H(3) (d), and 4-CF(3)C(6)H(4) (e)) in the presence of MeCN at ambient temperature generates (N-N)Pt(Ph)(NCMe)(+) (2). At -78 degrees C, protonation of 1a yielded (N-N)PtPh(2)(H)(NCMe)(+) (3a), which produced benzene and 2a at ca. -40 degrees C. Protonation of 1a-e in CD(2)Cl(2)/Et(2)O-d(10) furnished (N-N)Pt(C(6)H(5))(eta(2)-C(6)H(6))(+) (4a-e). The pi-benzene complexes 4a-c, sterically protected at Pt, eliminate benzene at ca. 0 degree C. The sterically less protected 4d-e lose benzene already at -30 degrees C. SST and 2D EXSY NMR demonstrate that phenyl and pi-benzene ligand protons undergo exchange with concomitant symmetrization of the diimine ligand, most likely via oxidative insertion of Pt into a C-H bond of coordinated benzene. The kinetics of the exchange processes for 4a-c were probed by quantitative EXSY spectroscopy, resulting in DeltaH() of 70-72 kJ mol(-1) and DeltaS of 37-48 J K(-1) mol(-1). A large, strongly temperature-dependent H/D kinetic isotope effect (9.7 at -34 degrees C; 6.9 at -19 degrees C) was measured for the dynamic behavior of 4a versus 4a-d(10), consistent with the proposed pi-benzene C-H bond cleavage. The fact that the pi-benzene complex 4a is thermally more robust in the absence of MeCN than is the Pt(IV) hydridodiphenyl complex 3a in the presence of MeCN agrees with the notion that arene elimination from Pt(IV) hydridoaryl complexes occurs via Pt(II) pi-arene intermediates that eliminate the hydrocarbon associatively, in this case, promoted by MeCN. Compounds 1a, 1b, 1d, 2a, and 2b have been crystallographically characterized. | 10.1021/ja056694z |
pubmed_565_16248 | Pollution is a major concern in urban areas. Due to its biological significance, genotoxicity should be a main focus for pollution biomonitoring, due mainly to the increasing complexity of the chemical environment in which organisms are exposed. Diluvio's Basin (Porto Alegre, RS, Brazil) is a heavily polluted urban ecosystem impacted by urban wastewater. Planarians are useful organism for evaluating environmental genotoxicity because of their high sensitivity, low cost, high proliferative rate and also because of their basal evolutionary position in relation to complex metazoans. Comet assay is a powerful and highly sensitive method of evaluating primary DNA lesions. Based on the unique features of planarians and the current environmental state of Diluvio's Basin, the aim of this work was to evaluate the genotoxic potential of this body of water using comet assay in planarians. Planarians were exposed to the water for 13 days in a laboratory and comet assay was performed in order to screen possible DNA damages. The results indicated an increasing gradient of damage towards basin's mouth. Such a gradient could be related to the gradual increase of pollutants among the different sample sites. Moreover, there seems to be a correlation between the urbanization gradient that exists within the watershed and the genotoxicity. Historical physical-chemical data was also gathered and examined for possible correlations with genotoxicity. Comet assay in planarians is a very promising test for environmental monitoring studies. Its application should be expanded. | 10.1016/j.mrgentox.2005.04.002 |
pubmed_538_4173 | BACKGROUND & AIMS
Functional dyspepsia (FD) is considered a heterogeneous disorder with different pathophysiological mechanisms contributing to the symptom pattern. The Rome II committee proposed that subdividing patients with FD into groups with predominant pain versus discomfort might identify subgroups with homogeneous pathophysiological and clinical properties. The aim of this study was to analyze the relationship of predominant pain or discomfort with pathophysiological mechanisms and to evaluate whether considering individual predominant symptoms yields better results.
METHODS
Consecutive FD patients (n = 720; 489 women; mean age, 41.3 +/- 0.6 years) filled out a dyspepsia questionnaire and identified a single most bothersome symptom. We analyzed the association of this predominant symptom with demographic, clinical, and pathophysiological features (Helicobacter pylori status, gastric emptying in 592 patients, and gastric sensitivity and accommodation testing in 332 patients).
RESULTS
According to Rome II criteria, 22% were pain predominant and 78% discomfort predominant. Patients with predominant pain had a higher prevalence of hypersensitivity (44% vs 25%) and delayed gastric emptying was observed less frequently in these patients (16% vs 26%), but there was major overlap. Detailed analysis showed that any of 8 dyspeptic symptoms could be predominant. Predominant early satiety or vomiting was associated with significantly higher prevalences of weight loss (89% and 75%, respectively) and of acute onset (61% and 60%, respectively). Impaired accommodation was found in 79% of patients with predominant early satiety. The highest prevalence of delayed emptying was found in predominant fullness (38%) and of hypersensitivity in predominant pain (44%).
CONCLUSIONS
Subdividing FD patient groups according to the predominant symptom does not reliably identify subgroups with a homogeneous underlying pathophysiological mechanism. | 10.1053/j.gastro.2005.10.019 |
pubmed_973_7715 | We developed a method for the determination of three aminothiols--cysteine, glutathione (GSH), and homocysteine--using surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS). The analytes were first captured using the unmodified 14-nm gold nanoparticles; N-2-mercaptopropionylglycine-modified gold nanoparticles serving as internal standard were sequentially added, and then the sample was analyzed using SALDI-MS. This approach provided good quantitative linearity of the three analytes (R(2) = approximately 0.99), with good reproducibility (relative standard deviations: <10%), in the analyses of GSH in the lysates of human red blood cells and MCF-7 cancer breast cells in the presence and absence of the anti-inflammatory drug sulfasalazine. The internal-standard SALDI-MS approach provides simplicity, accuracy, and precision to the determination of GSH in cells under drug invasion, to open an avenue for SALDI-MS to be used for the precise quantitative determination of a variety of analytes. From the clinical editor: This paper reports the development of a surface assisted laser desorption/ionization mass spectrometry method to precisely determine aminothiols-cysteine (Cys), glutathione (GSH), and homocysteine (HCys). | 10.1016/j.nano.2010.01.006 |
pubmed_884_8933 | Seasonal variations in the incidence of the conception of multiple pregnancies are compared in the same population area in two centuries. 12,617 singleton and 101 twin pregnancies from 1803 to 1852 are compared to 63,967 singleton, 473 twin and 5 triplet pregnancies from 1965 to 1970. In both groups the percentage decrease of multiple conceptions during the first three months of the year was higher than the percentage decrease of singleton conceptions. In both groups the percentage increase of multiple conceptions during the summer months was higher than the percentage increase of singleton conceptions. The question of the influence of light on the hypothalamic-pituitary centres as a cause of the variations in multiple conceptions is discussed. The incidence of multiple conceptions has decreased since the beginning of the 19th century independant of the progress in obstetrics and perinatology. The decreased rate of multiparas and especially older multiparas is suggested as the likely cause for this decrease. | pubmed_884_8933 |
pubmed_1052_19605 | PURPOSE
Intraductal pancreatic mucinous neoplasms (IPMN) are precancerous cystic lesions. The aim was to investigate the in situ IPMN proteome using MALDI (Matrix-Assisted Laser Desorption/Ionisation) imaging and to characterize biomarkers associated with the grade of dysplasia.
EXPERIMENTAL DESIGN
Frozen human Branch duct -IPMN sections were selected according to dysplasia and proteomic analyses were performed by MALDI imaging to obtain mass spectra distribution. The most discriminating peaks were identified using tissue extraction and nanoLC-ESI-MS/MS. Identified peaks were validated in independent series of IPMN by immunochemistry on surgical specimens (tissue-microarrays (TMA), n = 45) and endoscopic ultrasound fine-needle aspiration (EUS FNA) samples (n = 25).
RESULTS
BD-IPMN samples with low (n = 10) and high (n = 10) grades of dysplasia were analyzed. Differential spectra of proteins were found in the two groups with significantly different intensities (n = 15). The two peaks (intense in high grade IPMN) (m/z 8565 and 4747) were characterized as the monomeric ubiquitin (Mascot score = 319.22) and an acetylated fragment of thymosin-β4 (2-42) (Omssa score = 1.37 E-9). Validation on TMA and EUS FNA samples confirmed that ubiquitin was overexpressed in high grade dysplasia (p = 0.04 and p = 0.0004). Thymosin-β4 expression was confirmed on TMA by immunohistochemistry on high grade IPMN (p = 0.011).
CONCLUSION
Ubiquitin and thymosin-β4 are overexpressed in IPMN with high grade dysplasia. Positive immunochemical staining on EUS-FNA material is a major argument in support of preventive resection. | pubmed_1052_19605 |
pubmed_1133_23634 | Sustainable mesoporous graphitic carbon nitride (mpg-C3N4) modified PbBiO2Br porous microsphere (mpg-C3N4/PbBiO2Br) had been successfully synthesized via solvothermal process. Multiple techniques were applied to explore the structure, morphology, optical and electronic properties of the as-prepared photocatalysts. It could be found that the mpg-C3N4 was uniformly distributed on the surface of the PbBiO2Br porous microsphere. Compared with the pure PbBiO2Br, the mpg-C3N4/PbBiO2Br exhibited superior photocatalytic activity for the degradation of organic pollutants under visible light irradiation. When the mass fraction of mpg-C3N4 was 3%, the mpg-C3N4/PbBiO2Br composite materials exhibited the highest photocatalytic performance. The results indicated that the introduction of mpg-C3N4 could effectively enhance the electron mobility to promote the catalytic activity. The enhanced photocatalytic activity of the mpg-C3N4/PbBiO2Br materials can be attributed to the stronger optical trapping capability and the more effective separation efficiency of photogenerated electron-hole pairs. During the process of photocatalysis, the main active species of the photocatalysts were determined to be the and hole under visible light irradiation. Based on the relative band positions of mpg-C3N4 and PbBiO2Br, a possible photocatalytic mechanism of mpg-C3N4/PbBiO2Br composite catalyst was proposed. | 10.1016/j.jcis.2017.07.094 |
pubmed_357_20653 | Twelve new [11]-chaetoglobosins, chaetopseudeurins A-L (1-12), were identified from the fermentation of the endophytic fungus Pseudeurotium bakeri P1-1-1. Their structures with absolute configurations were elucidated by detailed interpretation of NMR spectroscopy, mass spectrometry, and single-crystal X-ray diffraction. Compounds 2 and 5-7 exhibited significant cytotoxicities against seven human cancer cell lines, with IC50 values ranging from 4.7 ± 1.0 to 12.2 ± 0.7 μM, and induced G2/M cell cycle arrest and apoptosis in MCF-7 and A427 cells dose dependently. Western blot analysis showed that compound 2 induced apoptosis of MCF-7 cells via the Bcl-2/caspase-3/PARP pathway. | 10.1021/acs.jnatprod.0c01335 |
pubmed_742_1465 | The water relations of growing epicotyl segments of pea (Pisum sativum L.) were studied using the miniaturized pressure probe. For epidermal cells stationary turgor pressures of P=5 to 9 bar and half-times of water exchange of individual cells T 1/2=1 to 27 s were found. The volumetric clastic modulus (ɛ) of epidermal cells varied from 12 to 200 bar and the hydraulic conductivity, Lp=0.2 to 2·10(-6) cm s(-1) bar(-1). For cortical cells P=5 to 11 bar, T 1/2=0.3 to 1 s, Lp=0.4 to 9·10(-5) cm s(-1) bar(-1) and ɛ=6 to 215 bar. The T 1/2 of cortical cells was extremely low and the Lp rather high as compared to other higher plant cells. The T 1/2-values of cortical cells were sometimes observed to change from short to substantially longer values (T 1/2=3 to 20 s). Both short and long pressure relaxations showed all the characteristics of non-artifactual curves. The change is apparently due to an increase in Lp and not ɛ, but the reason for the change in cell permeability to water is not known.In osmotic exchange experiments on peeled segments using solutions of different solutes, the half-time of osmotic water exchange for the whole segment was approximately 60 s. Water exchange occurred too quickly to be rate controlled by solute diffusion in the wall space. The data suggest that the short T 1/2-values in the cortical cells are the physiologically relevant ones for the intact tissue and that a considerable component of water transport occurs in the cell-to-cell pathway, although unstirred layer effects at the boundary between the segment and solution may influence the measured half-time. Using the theory of Molz and Boyer (1978, Plant Physiol. 62, 423-429), the gradient in water potential necessary to maintain the uptake of water for cell enlargement can be calculated from the measured diffusivities to be approximately 0.2 and 1 bar for growth rates of 1% h(-1) and 5% h(-1), respectively. Thus, although the T 1/2-values are short and Lp rather high, there may be a significant osmotic disequilibrium in the most rapidly growing tissue and as a consequence the influence of water transport on the growth rate cannot be excluded. | 10.1007/BF00384253 |
pubmed_531_4915 | Four modifications to the COSMIC molecular mechanics force field are described, which greatly increase both its versatility and the accuracy of calculated conformational energies. The Hill non-bonded van der Waals potential function has been replaced by a two-parameter Morse curve and a new H-H potential, similar to that in MM3, incorporated. Hydrocarbon energies in particular are much improved. A simple iterative Hückel pi-electron molecular orbital calculation allows modelling of conjugated systems. Calculated bond lengths and rotational barriers for a series of conjugated hydrocarbons and nitrogen heterocycles are shown to be as accurate as those determined by the MM2 SCF method. Explicit hydrogen-bonding potentials for H-bond acceptor-donor atom pairs have been included to give better hydrogen bond energies and lengths. The van der Waals radii of protonic hydrogens are reduced to 0.5 A and the energy well depth is increased to 1.0 kcal mol-1. Two new general atom types, N+sp2 and O-sp3, have been introduced which allow a wide variety of charged conjugated systems to be studied. A minimum of parameterisation is required, as the new types are easily included in the Hückel scheme which automatically adjusts bond and torsional parameters according to the defined bond-order relationships. | 10.1007/BF00125666 |
pubmed_1032_12899 | OBJECTIVE
Circulating immune-inflammatory cells have been increasingly recognized as robust prognostic biomarkers in cancer. Here, we sought to evaluate the prognostic values of preoperative peripheral platelet, neutrophil, lymphocyte quantitation in patients with primary oral squamous cell carcinoma (OSCC).
MATERIALS AND METHODS
A total number of 309 patients with primary OSCC surgically treated at our institutions were retrospectively included. Detailed demographic, clinicopathological, laboratory, and follow-up data were collected. The Kaplan-Meier analysis and Cox regression assay were performed to assess the prognostic values. A new prognostic risk score was developed and designed as PNL (platelet-neutrophil-lymphocyte) score based on combined preoperative platelets, neutrophils, and lymphocytes via calculating the regression coefficients of each type of cell by Cox regression analysis.
RESULTS
High platelet counts (≥266 × 109 /L), neutrophil counts (≥2.8 × 109 /L), PNL scores, and low lymphocyte counts (<1.4 × 109 /L) significantly associated with reduced overall and disease-free survival (Kaplan-Meier, p < 0.05, Log-rank test). Univariate and multivariate regression analyses revealed that individual platelet, neutrophil, lymphocyte quantitation, and PNL score were independent prognostic predictors for patient survival. Moreover, receiver operating characteristics curve revealed superior prognostic utility of PNL score for OSCC.
CONCLUSIONS
Our findings indicate that preoperative circulating platelets, neutrophils, lymphocytes, and PNL score serve as noninvasive, low-cost, and powerful prognostic predictors for patients with OSCC. | 10.1111/odi.13049 |
pubmed_270_18829 | Ethanol extracts of the aerial parts from five Labiatae (Lamiaceae) species, obtained from Antalya, Turkey, were tested for larvicidal activity against the house mosquito Culex pipiens L. (Diptera: Culicidae) under laboratory conditions. Third and fourth instar mortality from six concentrations (5, 10, 25, 50, 100 and 200 ppm) of each plant extract were compared against the organophosphorus insecticide, temephos which is currently used for larval control. All plant extracts showed high larvicidal activity in 24 h exposure tests. Teucrium divaricatum Sieber was the most toxic, followed by Mentha longifolia (L.) Huds., Melissa officinalis L., Salvia sclarea L. and Mentha pulegium L. with LC(50) values of 18.6, 26.8, 39.1, 62.7 and 81.0 ppm, respectively. This study is the first to report on the larvicidal activity of ethanol extracts of these five plant species against C. pipiens. | 10.1002/ptr.2004 |
pubmed_374_19201 | Common obstetrics and gynecology operations have different approaches and techniques and variations in the procedure. We aimed to discuss different approaches and variations in the techniques of the procedures as cystectomy, myomectomy, laparoscopy entry technique, sacrospinous ligament fixation, uretherocele, and rupture uterus. | 10.1007/s13193-019-00987-6 |
pubmed_1023_9343 | Different preimplantation surface finishes were applied to surgical vitallium discs and germanium prisms implanted for 20 days within the back muscles of adult rabbits. Histopathologic analysis of the numbers of nuclei of active fibroblasts immediately adjacent to the implants was carried out. The mean apparent volume fractions (MAVF) for the subdermal implant sites were found to depend on the surface cleanliness of the implant, the cleanest or highest-surface-energy surfaces giving the highest MAVF values for active fibroblasts. | 10.1111/j.1525-1594.1984.tb04252.x |
pubmed_304_2272 | Addictive drugs share with palatable food the property of increasing extracellular dopamine (DA), preferentially in the nucleus accumbens shell rather than in the core. However, by acting directly on the brain, drugs bypass the adaptive mechanisms (habituation) that constrain the responsiveness of accumbens shell DA to food reward, abnormally facilitating Pavlovian incentive learning and promoting the acquisition of abnormal DA-releasing properties by drug conditioned stimuli. Thus, whereas Pavlovian food conditioned stimuli release core but not shell DA, drug conditioned stimuli do the opposite, releasing shell but not core DA. This process, which results in the acquisition of excessive incentive-motivational properties by drug conditioned stimuli, initiates the drug addiction process. Neuroadaptive processes related to the chronic influence of drugs on subcortical DA might secondarily impair the function of prefronto-striatal loops, resulting in impairments in impulse control and decision making that form the basis for the compulsive feature of drug seeking and its relapsing character. | 10.1016/j.coph.2006.11.003 |
pubmed_579_6959 | PURPOSE
This study aimed to describe the efficacy of toric intraocular lenses (IOLs) in patients with low degrees of corneal astigmatism.
DESIGN
Retrospective case series was undertaken.
METHODS
Patients with low amounts of corneal astigmatism who were treated with either a toric monofocal lens (SN6AT2 Toric, n = 76) or a toric multifocal lens (SND1T2 +3.00, n = 44) were reviewed. Eyes were evaluated preoperatively and 3 months postoperatively. Refraction and visual outcomes were monitored.
RESULTS
Patients (69.7%) in the monofocal toric group obtained refractive cylinder less than 0.25 diopters (D) compared with 70.5% of the multifocal toric group. Both toric groups showed a statistically significant reduction in refractive cylinder after surgery (P = 0.001). Monofocal (66.7%) and multifocal (68.2%) toric patients achieved uncorrected distance visual acuity of 20/20 or better.
CONCLUSIONS
This represents the first article to investigate the use of low-power toric IOLs in patients with less than 1.25 D of corneal cylinder. Before the development of low-power toric IOLs, patients with low to moderate amounts of astigmatism required concurrent intraoperative adjustments or additional forms of treatment to benefit from cataract and IOL surgery. Evidence suggests that the toric T2 IOL now removes this barrier, providing consistent, accurate refractive and astigmatic results, and enables these patients to achieve excellent outcomes with a single treatment across IOL platforms. Larger studies will help to consolidate our results. | 10.1097/APO.0000000000000112 |
pubmed_400_3016 | Surfactin, an acidic lipopeptide produced by various strains of Bacillus subtilis, behaves as a very powerful biosurfactant and possesses several other interesting biological activities. This work deals with the molecular mechanism of membrane permeabilization by incorporation of surfactin. The surfactin-induced vesicle contents leakage was monitored by following release of carboxyfluorescein entrapped into unilamellar vesicles made of palmitoyloleoylphosphatidylcholine (POPC). The effect of the addition of cholesterol, dipalmitoylphosphatidylcholine (DPPC) and palmitoyloleoylphosphatidylethanolamine (POPE) was also checked. It was observed that surfactin was able to induce content leakage at concentrations far below the onset surfactin/lipid ratio for membrane solubilization to occur, which in our system was around 0.92. Electron microscopy showed that vesicles were present after addition of surfactin at a ratio below this value, whereas no vesicles could be observed at ratios above it. Cholesterol and POPE attenuated the membrane-perturbing effect of surfactin, whereas the effect of DPPC was to promote surfactin-induced leakage, indicating that bilayer sensitivity to surfactin increases with the lipid tendency to form lamellar phases, which is in agreement with our previous observation that surfactin destabilizes the inverted-hexagonal structure. Fourier-transform infrared spectroscopy (FTIR) was used to specifically follow the effect of surfactin on different parts of the phospholipid bilayer. The effect on the C=O stretching mode of vibration of POPC indicated a strong dehydration induced by surfactin. On the other hand, the C-H stretching bands showed that the lipopeptide interacts with the phospholipid acyl chains, resulting in considerable membrane fluidization. The reported effects could be useful to explain surfactin-induced 'pore' formation underlying the antibiotic and other important biological actions of this bacterial lipopeptide. | 10.1016/s0005-2736(03)00029-4 |
pubmed_494_2801 | Echinoderm early developmental stages might supply a good tool for toxicity testing in different fields, ranging from environment to food contamination, and in full respect of the 3Rs objectives (reduction, refinement, and replacement of animal experiments) that will eventually lead to the replacement of high vertebrate animal testing in toxicology. Sea urchin is one of the few organismic models considered by the European Agency for Alternative models. Actually, sea urchin embryonic development has been studied for over a century, and the complex nets of intercellular communications leading to the different events are well known, as well the possibility for environmental molecules and their residuals to interfere with such communications, causing developmental anomalies. In particular, the main goal of toxicologists since several years has been to establish a correlation between the cell-to-cell communications occurring during different developmental events and the signals occurring during neurogenesis, with the aim to pursue a mechanistic understanding of these processes and their deviations caused by stressors from different sources. | 10.1002/bdrc.20132 |
pubmed_137_5069 | Transition metal hexacyanoferrate/microporous activated carbon composites were obtained using a simple successive impregnation approach. The effect of metal type (nickel, indium, or copper), and the carbon oxidation on the composite characteristics (porosity, metal structure, and particle size), as well as on the removal efficiency of cesium from aqueous solution was investigated. Successful formation of the desired metal hexacyanoferrate phase was achieved and the size of the metallic nanoparticles and their dispersion in the carbon network was found to depend on the metal type, with the indium and nickel-based materials exhibiting the smallest particle size distribution (< 10 nm). Adsorption tests performed under batch conditions demonstrate that the copper hexacyanoferrate/activated carbon composite present the highest cesium removal capacity from aqueous solution (74.7 mg·g-1) among the three studied metal-based nanocomposites. The carbon oxidation treatment leads to the increase in the number of functional groups to the detriment of the porosity but allows for an improvement in the Cs adsorption capacity. This indicates that the Cs adsorption process is governed by the carbon surface chemistry and not its porosity. Moreover, combining oxidized carbon support with copper hexacyanoferrate induces the highest cesium adsorption capacity (101.5 mg·g-1). This could be related to synergistic effects through two absorption mechanisms, i.e., a cation exchange mechanism of Cs with the metallic hexacyanoferrate phase and Cs adsorption via carbon oxygen surface groups, as demonstrated using X-ray photoelectron spectroscopy (XPS) analyses. | 10.3390/ma12081253 |
pubmed_595_17597 | Biorthogonal Fourier series occur when applying separation of variables to many problems. Here an approach which possesses considerable advantages with respect to the standard one is explained. | 10.1073/pnas.78.12.7240 |
pubmed_631_2740 | This paper exploits the first two waves of NIDS to describe the socioeconomic profile of mortality and to assess whether self-rated health status is predictive of mortality between waves. Mortality rates in NIDS are in line with estimates from official death notification data and display the expected hump of excess mortality in early and middle adulthood due to AIDS, with the excess peaking earlier for women than for men. We find evidence of a socioeconomic gradient in mortality with higher rates of mortality for individuals from asset poor households and with lower levels of education. Consistent with evidence from many industrialized countries and a few developing countries, we find self-rated health to be a significant predictor of two year mortality, an association that remains after controlling for socioeconomic status and several other subjective and objective measures of health. | 10.1080/0376835X.2013.853611 |
pubmed_879_10722 | Humans and many animals have the ability to assess the confidence of their decisions. However, little is known about the underlying neural substrate and mechanism. In this study we propose a computational model consisting of a group of 'confidence neurons' with adaptation, which are able to assess the confidence of decisions by detecting the slope of ramping activities of decision neurons. The simulated activities of 'confidence neurons' in our simple model capture the typical features of confidence observed in humans and animals experiments. Our results indicate that confidence could be online formed along with the decision formation, and the adaptation properties could be used to monitor the formation of confidence during the decision making. | 10.1038/s41598-021-01523-9 |
pubmed_530_16135 | The generation of amyotrophic lateral sclerosis (ALS) disease models is an important subject for investigating disease mechanisms and pharmaceutical applications. In transgenic mice, expression of a mutant form of superoxide dismutase 1 (SOD1) can lead to the development of ALS that closely mimics the familial type of ALS (FALS). Although SOD1 mutant mice show phenotypes similar to FALS, dissimilar drug responses and size differences limit their usefulness to study the disease mechanism(s) and identify potential therapeutic compounds. Development of an in vitro model system for ALS is expected to help in obtaining novel insights into disease mechanisms and discovery of therapeutics. We report the establishment of an in vitro FALS model from human embryonic stem cells overexpressing either a wild-type (WT) or a mutant SOD1 (G93A) gene and the evaluation of the phenotypes and survival of the spinal motor neurons (sMNs), which are the neurons affected in ALS patients. The in vitro FALS model that we developed mimics the in vivo human ALS disease in terms of the following: (a) selective degeneration of sMNs expressing the G93A SOD1 but not those expressing the WT gene; (b) susceptibility of G93A SOD1-derived sMNs to form ubiquitinated inclusions; (c) astrocyte-derived factor(s) in the selective degeneration of G93A SOD1 sMNs; and (d) cell-autonomous, as well as non-cell-autonomous, dependent sMN degeneration. Thus, this model is expected to help unravel the disease mechanisms involved in the development of FALS and also lead to potential drug discoveries based on the prevention of neurodegeneration. | 10.5966/sctm.2011-0061 |
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